Implications for thymus growth in childhood: histogenesis of cortex and medulla
Tóm tắt
The increase in autoimmune diseases in recent years has drawn attention back to the thymus, with new approaches to improve and/or restore immune function being investigated. As the primary lymphoid organ responsible for functional T cell development, studies on the pre-/post-natal development of this organ and T lymphocytes in human and other species are of special interest. During our screening studies we observed structures that had not been described or mentioned previously, and named them “epitheliostromal sheaths”. Associated with these unique structures were also small attached lobules (possibly reflecting the maturational stages of thymic lobules), which the authors consider as markers of histogenesis and the growth of the organ during early childhood; these findings are thus presented to researchers in this field. Approximately 1000 sections prepared from infantile thymic tissues of partial biopsy specimens were immunostained and examined. Specimens were taken from ten patients (with informed consent) in the age range of 4–9 years who underwent surgery due to congenital cardiovascular anomalies but were otherwise normal. Digital images of interest were captured to describe them in detail. Determining the immunophenotype of the compartments in these newly developing lobules assisted us greatly in defining compartments and their growth order. In summary, our findings suggest a niche-based thymus growth mechanism during childhood. We presented our findings, hoping to provide additional insight to researchers aiming to restore thymus function in adulthood and improve its immunological functions.
Tài liệu tham khảo
Anderson G, Jenkinson E (1997) Piecing together the thymic puzzle. Immunol Today 18(8):363–364
Berzins SP, Uldrich AP, Sutherland JS et al (2002) Thymic regeneration: teaching an old immune system new tricks. Trends Mol Med 8(10):469–476
Blackburn CC, Augustine CL, Li R et al (1996) The nu gene acts cell-autonomously and is required for differentiation of thymic epithelial progenitors. Proc Natl Acad Sci USA 93(12):5742–5746
Bleul CC, Corbeaux T, Reuter A, Fisch P, Monting JS, Boehm T (2006) Formation of a functional thymus initiated by a postnatal epithelial progenitor cell. Nature 441(7096):992–996
Boehm T (2008) Thymus development and function. Curr Opin Immunol 20(2):178–184
Bruder D, Westendorf A, Hansen W et al (2005) On the edge of autoimmunity—T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes. Diabetes 54(12):3395–3401
Chinn IK, Blackburn CC, Manley NR, Sempowski GD (2012) Changes in primary lymphoid organs with aging. Semin Immunol 24(5):309–320
Dudakov JA, Khong DMP, Boyd RL, Chidgey AP (2010) Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution. Trends Immunol 31(5):191–198
Francis IR, Glazer GM, Bookstein FL, Gross BH (1985) The thymus—reexamination of age-related-changes in size and shape. AJR Am J Roentgenol 145(2):249–254
Gordon J, Manley NR (2011) Mechanisms of thymus organogenesis and morphogenesis. Development 138(18):3865–3878
Hamazaki Y, Sekai M, Minato N (2016) Medullary thymic epithelial stem cells: role in thymic epithelial cell maintenance and thymic involution. Immunol Rev 271(1):38–55
Heng TSP, Chidgey AP, Boyd RL (2010) Getting back at nature: understanding thymic development and overcoming its atrophy. Curr Opin Pharmacol 10(4):425–433
Hetzer-Egger C, Schorpp M, Haas-Assenbaum A, Balling R, Peters H, Boehm T (2002) Thymopoiesis requires Pax9 function in thymic epithelial cells. Eur J Immunol 32(4):1175–1181
Kaymaz FF, Dagdeviren A, Asan EA (2003) Antigenic profile of human thymus in concurrence with “Clusters of Thymic Epithelial Staining” classification. Ann Anat 185(2):163–171
Kishimoto T, Kikutani H, von dem Borne AEGK et al (1998) Leukocyte typing VI. Garland, New York
Kulida LV, Peretyatko LP, Nazarov SB (2015) Morphogenesis of human fetal thymus during weeks 22–27 of development. Russ J Dev Biol 46(4):208–214
Manley NR (2000) Thymus organogenesis and molecular mechanisms of thymic epithelial cell differentiation. Semin Immunol 12(5):421–428
Manley NR, Blackburn CC (2003) A developmental look at thymus organogenesis: where do the non-hematopoietic cells in the thymus come from? Curr Opin Immunol 15(2):225–232
Manley NR, Capecchi MR (1995) The role of hoxa-3 in mouse thymus and thyroid development. Development 121(7):1989–2003
Mansouri A, Goudreau G, Gruss P (1999) Pax genes and their role in organogenesis. Cancer Res 59(7):1707S–1709S
Mason D, Andre P, Bensussan A et al (2002) Leukocyte typing VII. Oxford University Press, Oxford
Munoz-Ruiz M, Sumaria N, Pennington DJ, Silva-Santos B (2017) Thymic determinants of gamma delta T cell differentiation. Trends Immunol 38(5):336–344
Parker GA, Picut CA, Swanson C, Toot JD (2015) Histologic features of postnatal development of immune system organs in the Sprague-Dawley rat. Toxicol Pathol 43(6):794–815
Peaudecerf L, Krenn G, Goncalves P, Vasseur F, Rocha B (2016) Thymocytes self-renewal: a major hope or a major threat? Immunol Rev 271(1):173–184
Prockop SE, Petrie HT (2004) Regulation of thymus size by competition for stromal niches among early T cell progenitors. J Immunol 173(3):1604–1611
Schlossman SF, Boumsell L, Gilks W et al (1995) Leukocyte typing V. Oxford University Press, Oxford
Serge A, Bailly AL, Aurrand-Lions M, Imhof BA, Irla M (2015) For3D: full organ reconstruction in 3D, an automatized tool for deciphering the complexity of lymphoid organs. J Immunol Methods 424:32–42
Shrimpton R, Butler M, Morel A, Eren E, Hue S, Ritter M (2009) CD205 (DEC-205): a recognition receptor for apoptotic and necrotic self. Mol Immunol 46(6):1229–1239
Sophia MM, Kalpana R (2016) Morphological and histological features of human fetal thymus gland. Int J Sci Study 4(8):187–191
Su DM, Ellis S, Napier A, Lee K, Manley NR (2001) Hoxa3 and Pax1 regulate epithelial cell death and proliferation during thymus and parathyroid organogenesis. Dev Biol 236(2):316–329
Takahama Y, Ohigashi I, Baik S, Anderson G (2017) Generation of diversity in thymic epithelial cells. Nat Rev Immunol 17(5):295–305
Tan SH, Nusse R (2017) In vivo lineage tracing reveals Axin2-expressing, long-lived cortical thymic epithelial progenitors in the postnatal thymus. PLoS One 12(9):12
Varga I, Pospisilova V, Jablonska-Mestanova V, Galfiova P, Polak S (2011) The thymus: picture review of human thymus prenatal development. Bratisl Lek Listy 112(7):368–376
Vasil’ev KA, Polevshchikov AV (2015) Thymus development in early ontogeny: a comparative aspect. Russ J Dev Biol 46(3):111–120
Ventevogel MS, Sempowski GD (2013) Thymic rejuvenation and aging. Curr Opin Immunol 25(4):516–522
Wallin J, Eibel H, Neubuser A, Wilting J, Koseki H, Balling R (1996) Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation. Development 122(1):23–30
Zhang LJ, Sun LG, Zhao Y (2007) Thymic epithelial progenitor cells and thymus regeneration: an update. Cell Res 17(1):50–55
Zola H, Swart B, Nicholson I et al (2005) CD molecules 2005: human cell differentiation molecules. Blood 106(9):3123–3126
