Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Các khía cạnh lâm sàng về sự gia tăng hoạt động ức chế miễn dịch liên quan đến tuổi tác
Tóm tắt
Quá trình lão hóa liên quan đến việc tái cấu trúc hệ thống miễn dịch, kèm theo tình trạng viêm mãn tính mức độ thấp và sự suy giảm dần chức năng của hệ thống miễn dịch. Những quá trình này còn được gọi là viêm lão hóa (inflammaging) và suy giảm miễn dịch (immunosenescence). Sự tái cấu trúc miễn dịch liên quan đến tuổi tác đi kèm với nhiều sự thay đổi lâm sàng, chẳng hạn như tăng nguy cơ mắc bệnh ung thư và các bệnh nhiễm trùng mãn tính, trong khi đó hiệu quả của việc tiêm phòng và liệu pháp miễn dịch giảm sút theo tuổi tác. Ngược lại, có bằng chứng thuyết phục cho thấy các trạng thái viêm mãn tính thúc đẩy quá trình lão hóa sớm. Tình trạng viêm liên quan đến quá trình lão hóa hoặc các điều kiện viêm mãn tính kích thích sự ức chế miễn dịch đối kháng, điều này bảo vệ các mô khỏi thương tổn viêm quá mức nhưng lại thúc đẩy suy giảm miễn dịch. Sự ức chế miễn dịch là một động lực trong các khối u và nhiễm trùng mãn tính, và nó cũng gây ra sự dung nạp đối với các loại vắc xin và liệu pháp miễn dịch. Các tế bào ức chế miễn dịch, chẳng hạn như các tế bào ức chế có nguồn gốc từ tủy xương (MDSC), tế bào T điều hòa (Treg) và đại thực bào loại M2, đóng vai trò quan trọng trong quá trình tạo khối u và nhiễm trùng mãn tính cũng như trong sự dung nạp đối với tiêm phòng và liệu pháp miễn dịch. Thú vị là, có nhiều bằng chứng cho thấy viêm lão hóa cũng liên quan đến hoạt động ức chế miễn dịch gia tăng, chẳng hạn như sự tăng biểu hiện của các tế bào ức chế miễn dịch và cytokine chống viêm. Với việc cả quá trình lão hóa và các trạng thái viêm mãn tính đều liên quan tới sự kích hoạt của sự ức chế miễn dịch và suy giảm miễn dịch, điều này có thể giải thích tại sao lão hóa lại là yếu tố rủi ro cho quá trình tạo khối u và các trạng thái viêm mãn tính, và ngược lại, các tác động viêm mãn tính thúc đẩy quá trình lão hóa sớm ở con người.
Từ khóa
#lão hóa #viêm lão hóa #suy giảm miễn dịch #ức chế miễn dịch #tế bào ức chế miễn dịch #ung thư #nhiễm trùng mãn tínhTài liệu tham khảo
Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann NY Acad Sci 908:244–254. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x
Benayoun BA, Pollina EA, Singh PP, Mahmoudi S, Harel I, Casey KM, Dulken BW, Kundaje A, Brunet A (2019) Remodeling of epigenome and transcriptome landscapes with aging in mice reveals widespread induction of inflammatory responses. Genome Res 29:697–709. https://doi.org/10.1101/gr.240093.118
Coppe JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5:99–118. https://doi.org/10.1146/annurev-pathol-121808-102144
Salminen A (2021) Increased immunosuppression impairs tissue homeostasis with aging and age-related diseases. J Mol Med (Berl) 99:1–20. https://doi.org/10.1007/s00109-020-01988-7
Salminen A (2021) Immunosuppressive network promotes immunosenescence associated with aging and chronic inflammatory conditions. J Mol Med (Berl) 99:1553–1569. https://doi.org/10.1007/s00109-021-02123-w
Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW et al (2019) Chronic inflammation in the etiology of disease across the life span. Nat Med 25:1822–1832. https://doi.org/10.1038/s41591-019-0675-0
Wang M, Jiang L, Monticone RE, Lakatta EG (2014) Proinflammation: the key to arterial aging. Trends Endocrinol Metab 25:72–79. https://doi.org/10.1016/j.tem.2013.10.002
Ebert T, Pawelzik SC, Witasp A, Arefin S, Hobson S, Kublickiene K, Shiels PG, Bäck M, Stenvinkel P (2020) Inflammation and premature ageing in chronic kidney disease. Toxins (Basel) 12:227. https://doi.org/10.3390/toxins12040227
Hou Y, Dan X, Babbar M, Wei Y, Hasselbalch SG, Croteau DL, Bohr VA (2019) Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 15:565–581. https://doi.org/10.1038/s41582-019-0244-7
Greten FR, Grivennikov SI (2019) Inflammation and cancer: Triggers, mechanisms, and consequences. Immunity 51:27–41. https://doi.org/10.1016/j.immuni.2019.06.025
Smetana K Jr, Lacina L, Szabo P, Dvorankova B, Broz P, Sedo A (2016) Ageing as an important risk factor for cancer. Anticancer Res 36:5009–5017. https://doi.org/10.21873/anticanres.11069
Marengoni A, Angleman S, Melis R, Mangialasche F, Karp A, Garmen A, Meinow B, Fratiglioni L (2011) Aging with multimorbidity: a systematic review of the literature. Ageing Res Rev 10:430–439. https://doi.org/10.1016/j.arr.2011.03.003
Belikov AV (2019) Age-related diseases as vicious cycles. Ageing Res Rev 49:11–26. https://doi.org/10.1016/j.arr.2018.11.002
De Martinis M, Franceschi C, Monti D, Ginaldi L (2006) Inflammation markers predicting frailty and mortality in the elderly. Exp Mol Pathol 80:219–227. https://doi.org/10.1016/j.yexmp.2005.11.004
Marcos-Perez D, Sanchez-Flores M, Proietti S, Bonassi S, Costa S, Teixeira JP, Fernandez-Tajes J, Pasaro E, Laffon B, Valdiglesias V (2020) Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis. Geroscience 42:1451–1473. https://doi.org/10.1007/s11357-020-00247-4
Arai Y, Martin-Ruiz CM, Takayama M, Abe Y, Takebayashi T, Koyasu S, Suematsu M, Hirose N, von Zglinicki T (2015) Inflammation, but not telomere length, predicts successful ageing at extreme old age: A longitudinal study of semi-supercentenarians. EBioMedicine 2:1549–1558. https://doi.org/10.1016/j.ebiom.2015.07.029
Rubino G, Bulati M, Aiello A, Aprile S, Gambino CM, Gervasi F, Caruso C, Accardi G (2019) Sicilian centenarian offspring are more resistant to immune ageing. Aging Clin Exp Res 31:125–133. https://doi.org/10.1007/s40520-018-0936-7
Bucci L, Ostan R, Cevenini E, Pini E, Scurti M, Vitale G, Mari D, Caruso C, Sansoni P, Fanelli F et al (2016) Centenarians’ offspring as a model of healthy aging: a reappraisal of the data on Italian subjects and a comprehensive overview. Aging (Albany NY) 8:510–519. https://doi.org/10.18632/aging.100912
Horvath S, Raj K (2018) DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet 19:371–384. https://doi.org/10.1038/s41576-018-0004-3
Horvath S, Pirazzini C, Bacalini MG, Gentilini D, Di Blasio AM, Delledonne M, Mari D, Arosio B, Monti D, Passarino G et al (2015) Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY) 7:1159–1170. https://doi.org/10.18632/aging.100861
Jylhävä J, Kananen L, Raitanen J, Marttila S, Nevalainen T, Hervonen A, Jylhä M, Hurme M (2016) Methylomic predictors demonstrate the role of NF-κB in old-age mortality and are unrelated to the aging-associated epigenetic drift. Oncotarget 7:19228–19241. https://doi.org/10.18632/oncotarget.8278
Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T (2008) Activation of innate immunity system during aging: NF-κB signaling is the molecular culprit of inflamm-aging. Ageing Res Rev 7:83–105. https://doi.org/10.1016/j.arr.2007.09.002
Clydesdale GJ, Dandie GW, Muller HK (2001) Ultraviolet light induced injury: immunological and inflammatory effects. Immunol Cell Biol 79:547–568. https://doi.org/10.1046/j.1440-1711.2001.01047.x
Bald T, Quast T, Landsberg J, Rogava M, Glodde N, Lopez-Ramos D, Kohlmeyer J, Riesenberg S, van den Boorn-Konijnenberg D, Hömig-Hölzel C et al (2014) Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507:109–113. https://doi.org/10.1038/nature13111
Fitsiou E, Pulido T, Campisi J, Alimirah F, Demaria M (2021) Cellular senescence and the senescence-associated secretory phenotype as drivers of skin photoaging. J Invest Dermatol 141:1119–1126. https://doi.org/10.1016/j.jid.2020.09.031
Lee YI, Choi S, Roh WS, Lee JH, Kim TG (2021) Cellular senescence and inflammaging in the skin microenvironment. Int J Mol Sci 22:3849. https://doi.org/10.3390/ijms22083849
Campisi J, Andersen JK, Kapahi P, Melov S (2011) Cellular senescence: a link between cancer and age-related degenerative disease? Semin Cancer Biol 21:354–359. https://doi.org/10.1016/j.semcancer.2011.09.001
Cupit-Link MC, Kirkland JL, Ness KK, Armstrong GT, Tchkonia T, LeBrasseur NK, Armenian SH, Ruddy KJ, Hashmi SK (2017) Biology of premature ageing in survivors of cancer. ESMO Open 2:e000250. https://doi.org/10.1136/esmoopen-2017-000250
Ness KK, Kirkland JL, Gramatges MM, Wang Z, Kundu M, McCastlain K, Li-Harms X, Zhang J, Tchkonia T, Pluijm SMF et al (2018) Premature physiologic aging as a paradigm for understanding increased risk of adverse health across the lifespan of survivors of childhood cancer. J Clin Oncol 36:2206–2215. https://doi.org/10.1200/JCO.2017.76.7467
Armenian SH, Gibson CJ, Rockne RC, Ness KK (2019) Premature aging in young cancer survivors. J Natl Cancer Inst 111:226–232. https://doi.org/10.1093/jnci/djy229
Derhovanessian E, Larbi A, Pawelec G (2009) Biomarkers of human immunosenescence: impact of cytomegalovirus infection. Curr Opin Immunol 21:440–445. https://doi.org/10.1016/j.coi.2009.05.012
Weltevrede M, Eilers R, de Melker HE, van Baarle D (2016) Cytomegalovirus persistence and T-cell immunosenescence in people aged fifty and older: A systematic review. Exp Gerontol 77:87–95. https://doi.org/10.1016/j.exger.2016.02.005
Hassouneh F, Goldeck D, Pera A, van Heemst D, Slagboom PE, Pawelec G, Solana R (2021) Functional changes of T-cell subsets with age and CMV infection. Int J Mol Sci 22:9973. https://doi.org/10.3390/ijms22189973
Kananen L, Nevalainen T, Jylhävä J, Marttila S, Hervonen A, Jylhä M, Hurme M (2015) Cytomegalovirus infection accelerates epigenetic aging. Exp Gerontol 72:227–229. https://doi.org/10.1016/j.exger.2015.10.008
Poloni C, Szyf M, Cheishvili D, Tsoukas CM (2022) Are the healthy vulnerable? Cytomegalovirus seropositivity in healthy adults is associated with accelerated epigenetic age and immune-dysregulation. J Infect Dis 225:443–452. https://doi.org/10.1093/infdis/jiab365
Aiello AE, Chiu YL, Frasca D (2017) How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms? Geroscience 39:261–271. https://doi.org/10.1007/s11357-017-9983-9
Kadambari S, Klenerman P, Pollard AJ (2020) Why the elderly appear to be more severely affected by COVID-19: The potential role of immunosenescence and CMV. Rev Med Virol 30:e2144. https://doi.org/10.1002/rmv.2144
Hearps AC, Martin GE, Rajasuriar R, Crowe SM (2014) Inflammatory co-morbidities in HIV+ individuals: learning lessons from healthy ageing. Curr HIV/AIDS Rep 11:20–34. https://doi.org/10.1007/s11904-013-0190-8
Nasi M, De Biasi S, Gibellini L, Bianchini E, Pecorini S, Bacca V, Guaraldi G, Mussini C, Pinti M, Cossarizza A (2017) Ageing and inflammation in patients with HIV infection. Clin Exp Immunol 187:44–52. https://doi.org/10.1111/cei.12814
Gianesin K, Noguera-Julian A, Zanchetta M, Del Bianco P, Petrara MR, Freguja R, Rampon O, Fortuny C, Camos M, Mozzo E et al (2016) Premature aging and immune senescence in HIV-infected children. AIDS 30:1363–1373. https://doi.org/10.1097/QAD.0000000000001093
Kooman JP, Dekker MJ, Usvyat LA, Kotanko P, van der Sande FM, Schalkwijk CG, Shiels PG, Stenvinkel P (2017) Inflammation and premature aging in advanced chronic kidney disease. Am J Physiol Renal Physiol 313:F938–F950. https://doi.org/10.1152/ajprenal.00256.2017
Barnes PJ (2017) Senescence in COPD and its comorbidities. Annu Rev Physiol 79:517–539. https://doi.org/10.1146/annurev-physiol-022516-034314
Chalan P, van den Berg A, Kroesen BJ, Brouwer L, Boots A (2015) Rheumatoid arthritis, immunosenescence and the hallmarks of aging. Curr Aging Sci 8:131–146. https://doi.org/10.2174/1874609808666150727110744
Betjes MG (2020) Uremia-associated ageing of the thymus and adaptive immune responses. Toxins (Basel) 12:224. https://doi.org/10.3390/toxins12040224
Zou D, Wu W, He Y, Ma S, Gao J (2018) The role of klotho in chronic kidney disease. BMC Nephrol 19:285. https://doi.org/10.1186/s12882-018-1094-z
Mytych J, Romerowicz-Misielak M, Koziorowski M (2018) Klotho protects human monocytes from LPS-induced immune impairment associated with immunosenescent-like phenotype. Mol Cell Endocrinol 470:1–13. https://doi.org/10.1016/j.mce.2017.05.003
Kuro-o M (2009) Klotho and aging. Biochim Biophys Acta 1790:1049–1058. https://doi.org/10.1016/j.bbagen.2009.02.005
Kanterman J, Sade-Feldman M, Baniyash M (2012) New insights into chronic inflammation-induced immunosuppression. Semin Cancer Biol 22:307–318. https://doi.org/10.1016/j.semcancer.2012.02.008
Amodio G, Cichy J, Conde P, Matteoli G, Moreau A, Ochando J, Oral BH, Pekarova M, Ryan EJ, Roth J et al (2019) Role of myeloid regulatory cells (MRCs) in maintaining tissue homeostasis and promoting tolerance in autoimmunity, inflammatory disease and transplantation. Cancer Immunol Immunother 68:661–672. https://doi.org/10.1007/s00262-018-2264-3
Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174. https://doi.org/10.1038/nri2506
Millrud CR, Bergenfelz C, Leandersson K (2017) On the origin of myeloid-derived suppressor cells. Oncotarget 8:3649–3665. https://doi.org/10.18632/oncotarget.12278
Murray PJ (2017) Macrophage polarization. Annu Rev Physiol 79:541–566. https://doi.org/10.1146/annurev-physiol-022516-034339
Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM, Chen SH (2006) Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 66:1123–1131. https://doi.org/10.1158/0008-5472.CAN-05-1299
Wang L, Zhao J, Ren JP, Wu XY, Morrison ZD, Elgazzar MA, Ning SB, Moorman JP, Yao ZQ (2016) Expansion of myeloid-derived suppressor cells promotes differentiation of regulatory T cells in HIV-1+ individuals. AIDS 30:1521–1531. https://doi.org/10.1097/QAD.0000000000001083
Clark RA (2010) Skin-resident T cells: the ups and downs of on site immunity. J Invest Dermatol 130:362–370. https://doi.org/10.1038/jid.2009.247
Zeng Q, Sun X, Xiao L, Xie Z, Bettini M, Deng T (2018) A unique population: Adipose-resident regulatory T cells. Front Immunol 9:2075. https://doi.org/10.3389/fimmu.2018.02075
Vignali DA, Collison LW, Workman CJ (2008) How regulatory T cells work. Nat Rev Immunol 8:523–532. https://doi.org/10.1038/nri2343
Sharma A, Rudra D (2018) Emerging functions of regulatory T cells in tissue homeostasis. Front Immunol 9:883. https://doi.org/10.3389/fimmu.2018.00883
Salminen A (2020) Activation of immunosuppressive network in the aging process. Ageing Res Rev 57:100998. https://doi.org/10.1016/j.arr.2019.100998
Kim R, Emi M, Tanabe K, Arihiro K (2006) Tumor-driven evolution of immunosuppressive networks during malignant progression. Cancer Res 66:5527–5536. https://doi.org/10.1158/0008-5472.CAN-05-4128
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23:549–555. https://doi.org/10.1016/s1471-4906(02)02302-5
Mauri C, Menon M (2015) The expanding family of regulatory B cells. Int Immunol 27:479–486. https://doi.org/10.1093/intimm/dxv038
Schmidt SV, Nino-Castro AC, Schultze JL (2012) Regulatory dendritic cells: there is more than just immune activation. Front Immunol 3:274. https://doi.org/10.3389/fimmu.2012.00274
Lünemann A, Lünemann JD, Münz C (2009) Regulatory NK-cell functions in inflammation and autoimmunity. Mol Med 15:352–358. https://doi.org/10.2119/molmed.2009.00035
Singh AK, Tripathi P, Cardell SL (2018) Type II NKT cells: An elusive population with immunoregulatory properties. Front Immunol 9:1969. https://doi.org/10.3389/fimmu.2018.01969
Li MO, Wan YY, Sanjabi S, Robertson AK, Flavell RA (2006) Transforming growth factor-β regulation of immune responses. Annu Rev Immunol 24:99–146. https://doi.org/10.1146/annurev.immunol.24.021605.090737
Murray PJ (2016) Amino acid auxotrophy as a system of immunological control nodes. Nat Immunol 17:132–139. https://doi.org/10.1038/ni.3323
Curdy N, Lanvin O, Laurent C, Fournie JJ, Franchini DM (2019) Regulatory mechanisms of inhibitory immune checkpoint receptors expression. Trends Cell Biol 29:777–790. https://doi.org/10.1016/j.tcb.2019.07.002
Sidler C, Woycicki R, Ilnytskyy Y, Metz G, Kovalchuk I, Kovalchuk O (2013) Immunosenescence is associated with altered gene expression and epigenetic regulation in primary and secondary immune organs. Front Genet 4:211. https://doi.org/10.3389/fgene.2013.00211
Gimenez JLG, Carbonell NE, Mateo CR, Lopez EG, Palacios L, Chova LP, Berenguer E, Garzo CG, Pallardo FV, Blanquer J (2016) Epigenetics as the driving force in long-term immunosuppression. J Clin Epigenet 2:2. https://doi.org/10.21767/2472-1158.100017
Motwani MP, Newson J, Kwong S, Richard-Loendt A, Colas R, Dalli J, Gilroy DW (2017) Prolonged immune alteration following resolution of acute inflammation in humans. PLoS ONE 12:e0186964. https://doi.org/10.1371/journal.pone.0186964
Newson J, Motwani MP, Kendall AC, Nicolaou A, Muccioli GG, Alhouayek M, Bennett M, Van De Merwe R, James S, De Maeyer RPH et al (2017) Inflammatory resolution triggers a prolonged phase of immune suppression through COX-1/mPGES-1-derived prostaglandin E2. Cell Rep 20:3162–3175. https://doi.org/10.1016/j.celrep.2017.08.098
Solana R, Pawelec G (1998) Molecular and cellular basis of immunosenescence. Mech Ageing Dev 102:115–129. https://doi.org/10.1016/s0047-6374(98)00029-3
Salminen A, Kaarniranta K, Kauppinen A (2019) Immunosenescence: the potential role of myeloid-derived suppressor cells (MDSC) in age-related immune deficiency. Cell Mol Life Sci 76:1901–1918. https://doi.org/10.1007/s00018-019-03048-x
Fulop T, Larbi A, Hirokawa K, Cohen AA, Witkowski JM (2020) Immunosenescence is both functional/adaptive and dysfunctional/maladaptive. Semin Immunopathol 42:521–536. https://doi.org/10.1007/s00281-020-00818-9
Ye J, Huang X, Hsueh EC, Zhang Q, Ma C, Zhang Y, Varvares MA, Hoft DF, Peng G (2012) Human regulatory T cells induce T-lymphocyte senescence. Blood 120:2021–2031. https://doi.org/10.1182/blood-2012-03-416040
Ghiringhelli F, Menard C, Terme M, Flament C, Taieb J, Chaput N, Puig PE, Novault S, Escudier B, Vivier E et al (2005) CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-β-dependent manner. J Exp Med 202:1075–1085. https://doi.org/10.1084/jem.20051511
Trzonkowski P, Szmit E, Mysliwska J, Mysliwski A (2006) CD4+CD25+ T regulatory cells inhibit cytotoxic activity of CTL and NK cells in humans - impact of immunosenescence. Clin Immunol 119:307–316. https://doi.org/10.1016/j.clim.2006.02.002
Hoechst B, Voigtlaender T, Ormandy L, Gamrekelashvili J, Zhao F, Wedemeyer H, Lehner F, Manns MP, Greten TF, Korangy F (2009) Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50:799–807. https://doi.org/10.1002/hep.23054
Crane CA, Han SJ, Barry JJ, Ahn BJ, Lanier LL, Parsa AT (2010) TGF-β downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Neuro Oncol 12:7–13. https://doi.org/10.1093/neuonc/nop009
Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, Herber DL, Schneck J, Gabrilovich DI (2007) Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 13:828–835. https://doi.org/10.1038/nm1609
Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22:275–281. https://doi.org/10.1016/j.semcancer.2012.01.011
Chou JP, Ramirez CM, Ryba DM, Koduri MP, Effros RB (2014) Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells. PLoS ONE 9:e99432. https://doi.org/10.1371/journal.pone.0099432
Hall BM, Balan V, Gleiberman AS, Strom E, Krasnov P, Virtuoso LP, Rydkina E, Vujcic S, Balan K, Gitlin I et al (2016) Aging of mice is associated with p16(Ink4a)- and β-galactosidase-positive macrophage accumulation that can be induced in young mice by senescent cells. Aging (Albany NY) 8:1294–1315. https://doi.org/10.18632/aging.100991
Fulop T, Dupuis G, Witkowski JM, Larbi A (2016) The role of immunosenescence in the development of age-related diseases. Rev Invest Clin 68:84–91
Barbe-Tuana F, Funchal G, Schmitz CRR, Maurmann RM, Bauer ME (2020) The interplay between immunosenescence and age-related diseases. Semin Immunopathol 42:545–557. https://doi.org/10.1007/s00281-020-00806-z
Bauer ME (2020) Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression. Immun Ageing 17:6. https://doi.org/10.1186/s12979-020-00178-w
Monneret G, Gossez M, Venet F (2021) Sepsis and immunosenescence: closely associated in a vicious circle. Aging Clin Exp Res 33:729–732. https://doi.org/10.1007/s40520-019-01350-z
Ovadya Y, Landsberger T, Leins H, Vadai E, Gal H, Biran A, Yosef R, Sagiv A, Agrawal A, Shapira A et al (2018) Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat Commun 9:5435. https://doi.org/10.1038/s41467-018-07825-3
Sagiv A, Biran A, Yon M, Simon J, Lowe SW, Krizhanovsky V (2013) Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 32:1971–1977. https://doi.org/10.1038/onc.2012.206
Sagiv A, Burton DG, Moshayev Z, Vadai E, Wensveen F, Ben-Dor S, Golani O, Polic B, Krizhanovsky V (2016) NKG2D ligands mediate immunosurveillance of senescent cells. Aging (Albany NY) 8:328–344. https://doi.org/10.18632/aging.100897
Della Chiesa M, Carlomagno S, Frumento G, Balsamo M, Cantoni C, Conte R, Moretta L, Moretta A, Vitale M (2006) The tryptophan catabolite L-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function. Blood 108:4118–4125. https://doi.org/10.1182/blood-2006-03-006700
Lazarova M, Steinle A (2019) Impairment of NKG2D-mediated tumor immunity by TGF-β. Front Immunol 10:2689. https://doi.org/10.3389/fimmu.2019.02689
Salminen A (2021) Feed-forward regulation between cellular senescence and immunosuppression promotes the aging process and age-related diseases. Ageing Res Rev 67:101280. https://doi.org/10.1016/j.arr.2021.101280
Callender LA, Carroll EC, Beal RWJ, Chambers ES, Nourshargh S, Akbar AN, Henson SM (2018) Human CD8+ EMRA T cells display a senescence-associated secretory phenotype regulated by p38 MAPK. Aging Cell 17:e12675. https://doi.org/10.1111/acel.12675
Pang WW, Price EA, Sahoo D, Beerman I, Maloney WJ, Rossi DJ, Schrier SL, Weissman IL (2011) Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc Natl Acad Sci U S A 108:20012–20017. https://doi.org/10.1073/pnas.1116110108
Enioutina EY, Bareyan D, Daynes RA (2011) A role for immature myeloid cells in immune senescence. J Immunol 186:697–707. https://doi.org/10.4049/jimmunol.1002987
Verschoor CP, Johnstone J, Millar J, Dorrington MG, Habibagahi M, Lelic A, Loeb M, Bramson JL, Bowdish DM (2013) Blood CD33+HLA-DR- myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol 93:633–637. https://doi.org/10.1189/jlb.0912461
Lages CS, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, Belkaid Y, Chougnet C (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181:1835–1848. https://doi.org/10.4049/jimmunol.181.3.1835
Flores RR, Clauson CL, Cho J, Lee BC, McGowan SJ, Baker DJ, Niedernhofer LJ, Robbins PD (2017) Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism. Aging Cell 16:480–487. https://doi.org/10.1111/acel.12571
Grizzle WE, Xu X, Zhang S, Stockard CR, Liu C, Yu S, Wang J, Mountz JD, Zhang HG (2007) Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice. Mech Ageing Dev 128:672–680. https://doi.org/10.1016/j.mad.2007.10.003
Garg SK, Delaney C, Toubai T, Ghosh A, Reddy P, Banerjee R, Yung R (2014) Aging is associated with increased regulatory T-cell function. Aging Cell 13:441–448. https://doi.org/10.1111/acel.12191
Shevach EM, Thornton AM (2014) tTregs, pTregs, and iTregs: similarities and differences. Immunol Rev 259:88–102. https://doi.org/10.1111/imr.12160
Jagger A, Shimojima Y, Goronzy JJ, Weyand CM (2014) Regulatory T cells and the immune aging process: a mini-review. Gerontology 60:130–137. https://doi.org/10.1159/000355303
Darrigues J, van Meerwijk JPM, Romagnoli P (2018) Age-dependent changes in regulatory T lymphocyte development and function: A mini-review. Gerontology 64:28–35. https://doi.org/10.1159/000478044
Szurek E, Cebula A, Wojciech L, Pietrzak M, Rempala G, Kisielow P, Ignatowicz L (2015) Differences in expression level of Helios and Neuropilin-1 do not distinguish thymus-derived from extrathymically-induced CD4+Foxp3+ regulatory T cells. PLoS ONE 10:e0141161. https://doi.org/10.1371/journal.pone.0141161
van der Geest KS, Abdulahad WH, Tete SM, Lorencetti PG, Horst G, Bos NA, Kroesen BJ, Brouwer E, Boots AM (2014) Aging disturbs the balance between effector and regulatory CD4+ T cells. Exp Gerontol 60:190–196. https://doi.org/10.1016/j.exger.2014.11.005
Ruhland MK, Loza AJ, Capietto AH, Luo X, Knolhoff BL, Flanagan KC, Belt BA, Alspach E, Leahy K, Luo J et al (2016) Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun 7:11762. https://doi.org/10.1038/ncomms11762
Feuerer M, Herrero L, Cipolletta D, Naaz A, Wong J, Nayer A, Lee J, Goldfine AB, Benoist C, Shoelson S et al (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15:930–939. https://doi.org/10.1038/nm.2002
Cipolletta D, Cohen P, Spiegelman BM, Benoist C, Mathis D (2015) Appearance and disappearance of the mRNA signature characteristic of Treg cells in visceral adipose tissue: age, diet, and PPARγ effects. Proc Natl Acad Sci U S A 112:482–487. https://doi.org/10.1073/pnas.1423486112
Kalathookunnel Antony A, Lian Z, Wu H (2018) T cells in adipose tissue in aging. Front Immunol 9:2945. https://doi.org/10.3389/fimmu.2018.02945
Bapat SP, Myoung Suh J, Fang S, Liu S, Zhang Y, Cheng A, Zhou C, Liang Y, LeBlanc M, Liddle C et al (2015) Depletion of fat-resident Treg cells prevents age-associated insulin resistance. Nature 528:137–141. https://doi.org/10.1038/nature16151
Jackaman C, Radley-Crabb HG, Soffe Z, Shavlakadze T, Grounds MD, Nelson DJ (2013) Targeting macrophages rescues age-related immune deficiencies in C57BL/6J geriatric mice. Aging Cell 12:345–357. https://doi.org/10.1111/acel.12062
Cui CY, Driscoll RK, Piao Y, Chia CW, Gorospe M, Ferrucci L (2019) Skewed macrophage polarization in aging skeletal muscle. Aging Cell 18:e13032. https://doi.org/10.1111/acel.13032
Duong L, Radley-Crabb HG, Gardner JK, Tomay F, Dye DE, Grounds MD, Pixley FJ, Nelson DJ, Jackaman C (2018) Macrophage depletion in elderly mice improves response to tumor immunotherapy, increases anti-tumor T cell activity and reduces treatment-induced cachexia. Front Genet 9:526. https://doi.org/10.3389/fgene.2018.00526
Shah KH, Shi P, Giani JF, Janjulia T, Bernstein EA, Li Y, Zhao T, Harrison DG, Bernstein KE, Shen XZ (2015) Myeloid suppressor cells accumulate and regulate blood pressure in hypertension. Circ Res 117:858–869. https://doi.org/10.1161/CIRCRESAHA.115.306539
Wang YG, Xiong X, Chen ZY, Liu KL, Yang JH, Wen Q, Wu FQ, Hu XF, Peng YD, Wu JJ et al (2015) Expansion of myeloid-derived suppressor cells in patients with acute coronary syndrome. Cell Physiol Biochem 35:292–304. https://doi.org/10.1159/000369696
Kuan R, Agrawal DK, Thankam FG (2021) Treg cells in atherosclerosis. Mol Biol Rep 48:4897–4910. https://doi.org/10.1007/s11033-021-06483-x
Wang H, Wang Z, Wu Q, Yuan Y, Cao W, Zhang X (2021) Regulatory T cells in ischemic stroke. CNS Neurosci Ther 27:643–651. https://doi.org/10.1111/cns.13611
Santamaria-Cadavid M, Rodriguez-Castro E, Rodriguez-Yanez M, Arias-Rivas S, Lopez-Dequidt I, Perez-Mato M, Rodriguez-Perez M, Lopez-Loureiro I, Hervella P, Campos F et al (2020) Regulatory T cells participate in the recovery of ischemic stroke patients. BMC Neurol 20:68. https://doi.org/10.1186/s12883-020-01648-w
Achmus L, Ruhnau J, Grothe S, von Sarnowski B, Bröker BM, Dressel A, Schulze J, Vogelgesang A (2020) Stroke-induced modulation of myeloid-derived suppressor cells (MDSCs) and IL-10-producing regulatory monocytes. Front Neurol 11:577971. https://doi.org/10.3389/fneur.2020.577971
Scrimini S, Pons J, Agusti A, Clemente A, Sallan MC, Bauca JM, Soriano JB, Cosio BG, Lopez M, Crespi C et al (2015) Expansion of myeloid-derived suppressor cells in chronic obstructive pulmonary disease and lung cancer: potential link between inflammation and cancer. Cancer Immunol Immunother 64:1261–1270. https://doi.org/10.1007/s00262-015-1737-x
Li XN, Pan X, Qiu D (2014) Imbalances of Th17 and Treg cells and their respective cytokines in COPD patients by disease stage. Int J Clin Exp Med 7:5324–5329
Hijona E, Hijona L, Arenas JI, Bujanda L (2010) Inflammatory mediators of hepatic steatosis. Mediators Inflamm 2010:837419. https://doi.org/10.1155/2010/837419
Zhou Z, Lai P, Zhang S, Wang Y, Qu N, Lu D, Gao L, Xu L, Yang Y, Zhang T et al (2021) The relationship between hepatic myeloid-derived suppressor cells and clinicopathological parameters in patients with chronic liver disease. Biomed Res Int 2021:6612477. https://doi.org/10.1155/2021/6612477
He B, Wu L, Xie W, Shao Y, Jiang J, Zhao Z, Yan M, Chen Z, Cui D (2017) The imbalance of Th17/Treg cells is involved in the progression of nonalcoholic fatty liver disease in mice. BMC Immunol 18:33. https://doi.org/10.1186/s12865-017-0215-y
Cairoli V, De Matteo E, Rios D, Lezama C, Galoppo M, Casciato P, Mullen E, Giadans C, Bertot G, Preciado MV et al (2021) Hepatic lymphocytes involved in the pathogenesis of pediatric and adult non-alcoholic fatty liver disease. Sci Rep 11:5129. https://doi.org/10.1038/s41598-021-84674-z
Dorhoi A, Du Plessis N (2018) Monocytic myeloid-derived suppressor cells in chronic infections. Front Immunol 8:1895. https://doi.org/10.3389/fimmu.2017.01895
Sarkar R, Mathew A, Sehrawat S (2019) Myeloid-derived suppressor cells confer infectious tolerance to dampen virus-induced tissue immunoinflammation. J Immunol 203:1325–1337. https://doi.org/10.4049/jimmunol.1900142
Rosado-Sanchez I, De Pablo-Bernal R, Rull A, Gonzalez J, Moreno S, Vinuesa D, Estrada V, Munoz-Fernandez MA, Vidal F, Leal M et al (2020) Increased frequencies of myeloid-derived suppressor cells precede immunodiscordance in HIV-infected subjects. Front Immunol 11:581307. https://doi.org/10.3389/fimmu.2020.581307
Hotchkiss RS, Monneret G, Payen D (2013) Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol 13:862–874. https://doi.org/10.1038/nri3552
Schrijver IT, Theroude C, Roger T (2019) Myeloid-derived suppressor cells in sepsis. Front Immunol 10:327. https://doi.org/10.3389/fimmu.2019.00327
Sacchi A, Grassi G, Bordoni V, Lorenzini P, Cimini E, Casetti R, Tartaglia E, Marchioni L, Petrosillo N, Palmieri F et al (2020) Early expansion of myeloid-derived suppressor cells inhibits SARS-CoV-2 specific T-cell response and may predict fatal COVID-19 outcome. Cell Death Dis 11:921. https://doi.org/10.1038/s41419-020-03125-1
Galvan-Pena S, Leon J, Chowdhary K, Michelson DA, Vijaykumar B, Yang L, Magnuson AM, Chen F, Manickas-Hill Z, Piechocka-Trocha A et al (2021) Profound Treg perturbations correlate with COVID-19 severity. Proc Natl Acad Sci USA 118:e2111315118. https://doi.org/10.1073/pnas.2111315118
Cunha LL, Perazzio SF, Azzi J, Cravedi P, Riella LV (2020) Remodeling of the immune response with aging: Immunosenescence and its potential impact on COVID-19 immune response. Front Immunol 11:1748. https://doi.org/10.3389/fimmu.2020.01748
Wang D, DuBois RN (2015) Immunosuppression associated with chronic inflammation in the tumor microenvironment. Carcinogenesis 36:1085–1093. https://doi.org/10.1093/carcin/bgv123
Elliott LA, Doherty GA, Sheahan K, Ryan EJ (2017) Human tumor-infiltrating myeloid cells: Phenotypic and functional diversity. Front Immunol 8:86. https://doi.org/10.3389/fimmu.2017.00086
Monteran L, Erez N (2019) The dark side of fibroblasts: Cancer-associated fibroblasts as mediators of immunosuppression in the tumor microenvironment. Front Immunol 10:1835. https://doi.org/10.3389/fimmu.2019.01835
Lian J, Yue Y, Yu W, Zhang Y (2020) Immunosenescence: a key player in cancer development. J Hematol Oncol 13:151. https://doi.org/10.1186/s13045-020-00986-z
Yang J, Liu M, Hong D, Zeng M, Zhang X (2021) The paradoxical role of cellular senescence in cancer. Front Cell Dev Biol 9:722205. https://doi.org/10.3389/fcell.2021.722205
Derhovanessian E, Solana R, Larbi A, Pawelec G (2008) Immunity, ageing and cancer. Immun Ageing 5:11. https://doi.org/10.1186/1742-4933-5-11
Fisher GJ, Kang S, Varani J, Bata-Csorgo Z, Wan Y, Datta S, Voorhees JJ (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138:1462–1470. https://doi.org/10.1001/archderm.138.11.1462
Halliday GM, Damian DL, Rana S, Byrne SN (2012) The suppressive effects of ultraviolet radiation on immunity in the skin and internal organs: implications for autoimmunity. J Dermatol Sci 66:176–182. https://doi.org/10.1016/j.jdermsci.2011.12.009
Prasad R, Katiyar SK (2017) Crosstalk among UV-induced inflammatory mediators, DNA damage and epigenetic regulators facilitates suppression of the immune system. Photochem Photobiol 93:930–936. https://doi.org/10.1111/php.12687
Hart PH, Norval M (2018) Ultraviolet radiation-induced immunosuppression and its relevance for skin carcinogenesis. Photochem Photobiol Sci 17:1872–1884. https://doi.org/10.1039/c7pp00312a
Soontrapa K, Honda T, Sakata D, Yao C, Hirata T, Hori S, Matsuoka T, Kita Y, Shimizu T, Kabashima K et al (2011) Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression. Proc Natl Acad Sci U S A 108:6668–6673. https://doi.org/10.1073/pnas.1018625108
Skobowiat C, Postlethwaite AE, Slominski AT (2017) Skin exposure to ultraviolet B rapidly activates systemic neuroendocrine and immunosuppressive responses. Photochem Photobiol 93:1008–1015. https://doi.org/10.1111/php.12642
Schwarz T (2005) Regulatory T cells induced by ultraviolet radiation. Int Arch Allergy Immunol 137:187–193. https://doi.org/10.1159/000086330
Maeda A, Beissert S, Schwarz T, Schwarz A (2008) Phenotypic and functional characterization of ultraviolet radiation-induced regulatory T cells. J Immunol 180:3065–3071. https://doi.org/10.4049/jimmunol.180.5.3065
Ali N, Rosenblum MD (2017) Regulatory T cells in skin Immunology 152:372–381. https://doi.org/10.1111/imm.12791
Navid F, Bruhs A, Schuller W, Fritsche E, Krutmann J, Schwarz T, Schwarz A (2013) The aryl hydrocarbon receptor is involved in UVR-induced immunosuppression. J Invest Dermatol 133:2763–2770. https://doi.org/10.1038/jid.2013.221
Fritsche E, Schäfer C, Calles C, Bernsmann T, Bernshausen T, Wurm M, Hübenthal U, Cline JE, Hajimiragha H, Schroeder P et al (2007) Lightening up the UV response by identification of the aryl hydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc Natl Acad Sci U S A 104:8851–8856. https://doi.org/10.1073/pnas.0701764104
Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA (2010) An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 185:3190–3198. https://doi.org/10.4049/jimmunol.0903670
Hidaka T, Fujimura T, Aiba S (2019) Aryl hydrocarbon receptor modulates carcinogenesis and maintenance of skin cancers. Front Med (Lausanne) 6:194. https://doi.org/10.3389/fmed.2019.00194
Okuma A, Hanyu A, Watanabe S, Hara E (2017) p16Ink4a and p21Cip1/Waf1 promote tumour growth by enhancing myeloid-derived suppressor cells chemotaxis. Nat Commun 8:2050. https://doi.org/10.1038/s41467-017-02281-x
Ladomersky E, Scholtens DM, Kocherginsky M, Hibler EA, Bartom ET, Otto-Meyer S, Zhai L, Lauing KL, Choi J, Sosman JA et al (2019) The coincidence between increasing age, immunosuppression, and the incidence of patients with glioblastoma. Front Pharmacol 10:200. https://doi.org/10.3389/fphar.2019.00200
Salminen A, Kaarniranta K, Hiltunen M, Kauppinen A (2014) Histone demethylase Jumonji D3 (JMJD3/KDM6B) at the nexus of epigenetic regulation of inflammation and the aging process. J Mol Med (Berl) 92:1035–1043. https://doi.org/10.1007/s00109-014-1182-x
Zhao Y, Forst CV, Sayegh CE, Wang IM, Yang X, Zhang B (2016) Molecular and genetic inflammation networks in major human diseases. Mol Biosyst 12:2318–2341. https://doi.org/10.1039/c6mb00240d
Perna L, Zhang Y, Mons U, Holleczek B, Saum KU, Brenner H (2016) Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort. Clin Epigenetics 8:64. https://doi.org/10.1186/s13148-016-0228-z
Zheng C, Berger NA, Li L, Xu R (2020) Epigenetic age acceleration and clinical outcomes in gliomas. PLoS ONE 15:e0236045. https://doi.org/10.1371/journal.pone.0236045
Pera A, Campos C, Lopez N, Hassouneh F, Alonso C, Tarazona R, Solana R (2015) Immunosenescence: Implications for response to infection and vaccination in older people. Maturitas 82:50–55. https://doi.org/10.1016/j.maturitas.2015.05.004
Channappanavar R, Perlman S (2020) Age-related susceptibility to coronavirus infections: role of impaired and dysregulated host immunity. J Clin Invest 130:6204–6213. https://doi.org/10.1172/JCI144115
Uyemura K, Castle SC, Makinodan T (2002) The frail elderly: role of dendritic cells in the susceptibility of infection. Mech Ageing Dev 123:955–962. https://doi.org/10.1016/s0047-6374(02)00033-7
Frasca D, Blomberg BB (2020) Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination. Immun Ageing 17:37. https://doi.org/10.1186/s12979-020-00210-z
Simmons SR, Bhalla M, Herring SE, Tchalla EYI, Bou Ghanem EN (2021) Older but not wiser: the age-driven changes in neutrophil responses during pulmonary infections. Infect Immun 89:e00653-e720. https://doi.org/10.1128/IAI.00653-20
Goronzy JJ, Hu B, Kim C, Jadhav RR, Weyand CM (2018) Epigenetics of T cell aging. J Leukoc Biol 104:691–699. https://doi.org/10.1002/JLB.1RI0418-160R
Rodriguez RM, Saiz ML, Suarez-Alvarez B, Lopez-Larrea C (2022) Epigenetic networks driving T cell identity and plasticity during immunosenescence. Trends Genet 38:120–123. https://doi.org/10.1016/j.tig.2021.08.014
Aspinall R, Del Giudice G, Effros RB, Grubeck-Loebenstein B, Sambhara S (2007) Challenges for vaccination in the elderly. Immun Ageing 4:9. https://doi.org/10.1186/1742-4933-4-9
Chen S, Akbar SM, Miyake T, Abe M, Al-Mahtab M, Furukawa S, Bunzo M, Hiasa Y, Onji M (2015) Diminished immune response to vaccinations in obesity: role of myeloid-derived suppressor and other myeloid cells. Obes Res Clin Pract 9:35–44. https://doi.org/10.1016/j.orcp.2013.12.006
Merani S, Pawelec G, Kuchel GA, McElhaney JE (2017) Impact of aging and cytomegalovirus on immunological response to influenza vaccination and infection. Front Immunol 8:784. https://doi.org/10.3389/fimmu.2017.00784
Corsini E, Vismara L, Lucchi L, Viviani B, Govoni S, Galli CL, Marinovich M, Racchi M (2006) High interleukin-10 production is associated with low antibody response to influenza vaccination in the elderly. J Leukoc Biol 80:376–382. https://doi.org/10.1189/jlb.0306190
Batista-Duharte A, Pera A, Alino SF, Solana R (2021) Regulatory T cells and vaccine effectiveness in older adults. Challenges and prospects Int Immunopharmacol 96:107761. https://doi.org/10.1016/j.intimp.2021.107761
Iclozan C, Antonia S, Chiappori A, Chen DT, Gabrilovich D (2013) Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer. Cancer Immunol Immunother 62:909–918. https://doi.org/10.1007/s00262-013-1396-8
Hamilton JAG, Henry CJ (2020) Aging and immunotherapies: New horizons for the golden ages. Cancer Aging 1:30–44. https://doi.org/10.1002/aac2.12014
Elias R, Karantanos T, Sira E, Hartshorn KL (2017) Immunotherapy comes of age: Immune aging & checkpoint inhibitors. J Geriatr Oncol 8:229–235. https://doi.org/10.1016/j.jgo.2017.02.001
Hegde PS, Chen DS (2020) Top 10 challenges in cancer immunotherapy. Immunity 52:17–35. https://doi.org/10.1016/j.immuni.2019.12.011
Fleming V, Hu X, Weber R, Nagibin V, Groth C, Altevogt P, Utikal J, Umansky V (2018) Targeting myeloid-derived suppressor cells to bypass tumor-induced immunosuppression. Front Immunol 9:398. https://doi.org/10.3389/fimmu.2018.00398
Kim JH, Kim BS, Lee SK (2020) Regulatory T cells in tumor microenvironment and approach for anticancer immunotherapy. Immune Netw 20:e4. https://doi.org/10.4110/in.2020.20.e4
Hou A, Hou K, Huang Q, Lei Y, Chen W (2020) Targeting myeloid-derived suppressor cell, a promising strategy to overcome resistance to immune checkpoint inhibitors. Front Immunol 11:783. https://doi.org/10.3389/fimmu.2020.00783
Fultang L, Panetti S, Ng M, Collins P, Graef S, Rizkalla N, Booth S, Lenton R, Noyvert B, Shannon-Lowe C et al (2019) MDSC targeting with Gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers. EBioMedicine 47:235–246. https://doi.org/10.1016/j.ebiom.2019.08.025
Zou S, Tong Q, Liu B, Huang W, Tian Y, Fu X (2020) Targeting STAT3 in cancer immunotherapy. Mol Cancer 19:145. https://doi.org/10.1186/s12943-020-01258-7
Bauer R, Udonta F, Wroblewski M, Ben-Batalla I, Santos IM, Taverna F, Kuhlencord M, Gensch V, Päsler S, Vinckier S et al (2018) Blockade of myeloid-derived suppressor cell expansion with all-trans retinoic acid increases the efficacy of antiangiogenic therapy. Cancer Res 78:3220–3232. https://doi.org/10.1158/0008-5472.CAN-17-3415
Salminen A, Kaarniranta K, Kauppinen A (2018) Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders. Int Immunopharmacol 61:231–240. https://doi.org/10.1016/j.intimp.2018.06.005
Hurez V, Daniel BJ, Sun L, Liu AJ, Ludwig SM, Kious MJ, Thibodeaux SR, Pandeswara S, Murthy K, Livi CB et al (2012) Mitigating age-related immune dysfunction heightens the efficacy of tumor immunotherapy in aged mice. Cancer Res 72:2089–2099. https://doi.org/10.1158/0008-5472.CAN-11-3019
Krstic J, Santibanez JF (2014) Transforming growth factor-β and matrix metalloproteinases: functional interactions in tumor stroma-infiltrating myeloid cells. ScientificWorldJournal 2014:521754. https://doi.org/10.1155/2014/521754
Meng XM, Nikolic-Paterson DJ, Lan HY (2016) TGF-β: the master regulator of fibrosis. Nat Rev Nephrol 12:325–338. https://doi.org/10.1038/nrneph.2016.48
Tominaga K, Suzuki HI (2019) TGF-β signaling in cellular senescence and aging-related pathology. Int J Mol Sci 20:5002. https://doi.org/10.3390/ijms20205002
Wu TT, Li WM, Yao YM (2016) Interactions between autophagy and inhibitory cytokines. Int J Biol Sci 12:884–897. https://doi.org/10.7150/ijbs.15194
Ohl K, Tenbrock K (2018) Reactive oxygen species as regulators of MDSC-mediated immune suppression. Front Immunol 9:2499. https://doi.org/10.3389/fimmu.2018.02499
Heinbokel T, Elkhal A, Liu G, Edtinger K, Tullius SG (2013) Immunosenescence and organ transplantation Transplant Rev (Orlando) 27:65–75. https://doi.org/10.1016/j.trre.2013.03.001
Krenzien F, ElKhal A, Quante M, Rodriguez Cetina Biefer H, Hirofumi U, Gabardi S, Tullius SG (2015) A rationale for age-adapted immunosuppression in organ transplantation. Transplantation 99:2258–2268. https://doi.org/10.1097/TP.0000000000000842
Cao P, Sun Z, Feng C, Zhang J, Zhang F, Wang W, Zhao Y (2020) Myeloid-derived suppressor cells in transplantation tolerance induction. Int Immunopharmacol 83:106421. https://doi.org/10.1016/j.intimp.2020.106421
Lee WC, Wang YC, Hsu HY, Hsu PY, Cheng CH, Lee CF, Wu TJ, Chan KM (2021) Immunological discrepancy in aged mice facilitates skin allograft survival. Aging (Albany NY) 13:16219–16228. https://doi.org/10.18632/aging.203152
Dayoub JC, Cortese F, Anzic A, Grum T, de Magalhaes JP (2018) The effects of donor age on organ transplants: A review and implications for aging research. Exp Gerontol 110:230–240. https://doi.org/10.1016/j.exger.2018.06.019
Trzonkowski P, Debska-Slizien A, Jankowska M, Wardowska A, Carvalho-Gaspar M, Hak L, Moszkowska G, Bzoma B, Mills N, Wood KJ et al (2010) Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells. Mech Ageing Dev 131:96–104. https://doi.org/10.1016/j.mad.2009.12.006
Martins PN, Tullius SG, Markmann JF (2014) Immunosenescence and immune response in organ transplantation. Int Rev Immunol 33:162–173. https://doi.org/10.3109/08830185.2013.829469
Ferrer IR, Hester J, Bushell A, Wood KJ (2014) Induction of transplantation tolerance through regulatory cells: from mice to men. Immunol Rev 258:102–116. https://doi.org/10.1111/imr.12158
Rickert CG, Markmann JF (2019) Current state of organ transplant tolerance. Curr Opin Organ Transplant 24:441–450. https://doi.org/10.1097/MOT.0000000000000670
Thewissen M, Linsen L, Somers V, Geusens P, Raus J, Stinissen P (2005) Premature immunosenescence in rheumatoid arthritis and multiple sclerosis patients. Ann NY Acad Sci 1051:255–262. https://doi.org/10.1196/annals.1361.066
Goronzy JJ, Li G, Yang Z, Weyand CM (2013) The janus head of T cell aging - autoimmunity and immunodeficiency. Front Immunol 4:131. https://doi.org/10.3389/fimmu.2013.00131
Watad A, Bragazzi NL, Adawi M, Amital H, Toubi E, Porat BS, Shoenfeld Y (2017) Autoimmunity in the elderly: Insights from basic science and clinics - A mini-review. Gerontology 63:515–523. https://doi.org/10.1159/000478012
Barnie PA, Zhang P, Lv H, Wang D, Su X, Su Z, Xu H (2017) Myeloid-derived suppressor cells and myeloid regulatory cells in cancer and autoimmune disorders. Exp Ther Med 13:378–388. https://doi.org/10.3892/etm.2016.4018
Wegner A, Verhagen J, Wraith DC (2017) Myeloid-derived suppressor cells mediate tolerance induction in autoimmune disease. Immunology 151:26–42. https://doi.org/10.1111/imm.12718
Li M, Zhu D, Wang T, Xia X, Tian J, Wang S (2018) Roles of myeloid-derived suppressor cell subpopulations in autoimmune arthritis. Front Immunol 9:2849. https://doi.org/10.3389/fimmu.2018.02849
Eggenhuizen PJ, Ng BH, Ooi JD (2020) Treg enhancing therapies to treat autoimmune diseases. Int J Mol Sci 21:7015. https://doi.org/10.3390/ijms21197015
Selck C, Dominguez-Villar M (2021) Antigen-specific regulatory T cell therapy in autoimmune diseases and transplantation. Front Immunol 12:661875. https://doi.org/10.3389/fimmu.2021.661875
Zhang Q, Lu W, Liang CL, Chen Y, Liu H, Qiu F, Dai Z (2018) Chimeric antigen receptor (CAR) Treg: A promising approach to inducing immunological tolerance. Front Immunol 9:2359. https://doi.org/10.3389/fimmu.2018.02359
