Nutritional Modulation of Immune Function: Analysis of Evidence, Mechanisms, and Clinical Relevance

Baeke, 2010, Vitamin D: modulator of the immune system, Curr Opin Pharmacol., 10, 482, 10.1016/j.coph.2010.04.001

Gombart, 2009, The vitamin D-antimicrobial peptide pathway and its role in protection against infection, Future Microbiol., 4, 1151, 10.2217/fmb.09.87

Ohta, 1985, 1 alpha,25-Dihydroxyvitamin D3 (calcitriol) stimulates proliferation of human circulating monocytes in vitro, FEBS Lett., 185, 9, 10.1016/0014-5793(85)80730-4

Xu, 1993, 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes, Scand J Immunol., 38, 535, 10.1111/j.1365-3083.1993.tb03237.x

Gombart, 2005, Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3, FASEB J., 19, 1067, 10.1096/fj.04-3284com

Liu, 2006, Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science, 311, 1770, 10.1126/science.1123933

Wang, 2004, Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression, J Immunol., 173, 2909, 10.4049/jimmunol.173.5.2909

Provvedini, 1983, 1,25-dihydroxyvitamin D3 receptors in human leukocytes, Science, 221, 1181, 10.1126/science.6310748

Lemire, 1984, 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells, J Clin Invest., 74, 657, 10.1172/JCI111465

Rigby, 1984, Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol), J Clin Invest., 74, 1451, 10.1172/JCI111557

Kongsbak, 2013, The vitamin d receptor and T cell function, Front Immunol., 4, 148, 10.3389/fimmu.2013.00148

Mora, 2008, Vitamin effects on the immune system: vitamins A and D take centre stage, Nat Rev Immunol., 8, 685, 10.1038/nri2378

Rigby, 1987, Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA, J Clin Invest., 79, 1659, 10.1172/JCI113004

Alroy, 1995, Transcriptional repression of the interleukin-2 gene by vitamin D3: direct inhibition of NFATp/AP-1 complex formation by a nuclear hormone receptor, Mol Cell Biol., 15, 5789, 10.1128/MCB.15.10.5789

Cippitelli, 1998, Vitamin D3: a transcriptional modulator of the interferon-gamma gene, Eur J Immunol., 28, 3017, 10.1002/(SICI)1521-4141(199810)28:10<3017::AID-IMMU3017>;3.0.CO;2-6

Wei, 2015, Mechanisms underlying the regulation of innate and adaptive immunity by Vitamin D, Nutrients, 7, 8251, 10.3390/nu7105392

Bscheider, 2016, Vitamin D immunoregulation through dendritic cells, Immunology, 148, 227, 10.1111/imm.12610

Penna, 2000, 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation, J Immunol., 164, 2405, 10.4049/jimmunol.164.5.2405

Kearns, 2015, Impact of vitamin D on infectious disease, Am J Med Sci., 349, 245, 10.1097/MAJ.0000000000000360

Kroner, 2015, Vitamin D every day to keep the infection away?, Nutrients, 7, 4170, 10.3390/nu7064170

Zittermann, 2016, Vitamin D and airway infections: a European perspective, Eur J Med Res., 21, 14, 10.1186/s40001-016-0208-y

Colotta, 2017, Modulation of inflammatory and immune responses by vitamin D, J Autoimmun., 85, 78, 10.1016/j.jaut.2017.07.007

Dankers, 2016, Vitamin D in autoimmunity: molecular mechanisms and therapeutic potential, Front Immunol., 7, 697, 10.3389/fimmu.2016.00697

Agmon-Levin, 2013, Vitamin D in systemic and organ-specific autoimmune diseases, Clin Rev Allergy Immunol., 45, 256, 10.1007/s12016-012-8342-y

Antico, 2012, Can supplementation with vitamin D reduce the risk or modify the course of autoimmune diseases? A systematic review of the literature, Autoimmun Rev., 12, 127, 10.1016/j.autrev.2012.07.007

Coquette, 1986, Role of vitamin E in the protection of the resident macrophage membrane against oxidative damage, Arch Int Physiol Biochim., 94, S29

Hatam, 1979, A high-performance liquid chromatographic method for the determination of tocopherol in plasma and cellular elements of the blood, J Lipid Res., 20, 639, 10.1016/S0022-2275(20)40587-5

Eskew, 1985, Effects of vitamin E and selenium deficiencies on rat immune function, Immunology, 54, 173

Langweiler, 1981, Effect of vitamin E deficiency on the proliferative response of canine lymphocytes, Am J Vet Res., 42, 1681

Turner, 1990, Immunological malfunctions associated with low selenium-vitamin E diets in lambs, J Comp Pathol., 102, 99, 10.1016/S0021-9975(08)80012-6

Jensen, 1988, The effect of vitamin E on the cell-mediated immune response in pigs, Zentralbl Veterinarmed B, 35, 549, 10.1111/j.1439-0450.1988.tb00528.x

Chang, 1994, Effect of dietary vitamin E and selenium deficiency on chicken splenocyte proliferation and cell surface marker expression, Immunopharmacol Immunotoxicol., 16, 203, 10.3109/08923979409007091

Meydani, 1986, Vitamin E supplementation suppresses prostaglandin E1(2) synthesis and enhances the immune response of aged mice, Mech Ageing Dev., 34, 191, 10.1016/0047-6374(86)90034-5

Sakai, 1997, Long-term feeding of high vitamin E diet improves the decreased mitogen response of rat splenic lymphocytes with aging, J Nutr Sci Vitaminol., 43, 113, 10.3177/jnsv.43.113

Meydani, 1990, Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects, Am J Clin Nutr., 52, 557, 10.1093/ajcn/52.3.557

Meydani, 1997, Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial, JAMA, 277, 1380, 10.1001/jama.1997.03540410058031

Pallast, 1999, Effect of 50- and 100-mg vitamin E supplements on cellular immune function in noninstitutionalized elderly persons, Am J Clin Nutr., 69, 1273, 10.1093/ajcn/69.6.1273

Meydani, 2005, Vitamin E and immune response in the aged: molecular mechanisms and clinical implications, Immunol Rev., 205, 269, 10.1111/j.0105-2896.2005.00274.x

Wu, 2008, Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention, J Leukoc Biol., 84, 900, 10.1189/jlb.0108023

Adolfsson, 2001, Vitamin E-enhanced IL-2 production in old mice: naive but not memory T cells show increased cell division cycling and IL-2-producing capacity, J Immunol., 167, 3809, 10.4049/jimmunol.167.7.3809

Marko, 2007, Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation, J Immunol., 178, 1443, 10.4049/jimmunol.178.3.1443

Marko, 2009, Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice, J Nutr., 139, 1192, 10.3945/jn.108.103416

Smith, 1971, Cyclic adenosine 3′,5′-monophosphate in human lymphocytes, . J Clin Invest., 50, 432, 10.1172/JCI106510

Smith, 1971, Human lymphocytic metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin, J Clin Invest., 50, 442, 10.1172/JCI106511

Harris, 2002, Prostaglandins as modulators of immunity, Trends Immunol., 23, 144, 10.1016/S1471-4906(01)02154-8

Kalinski, 2012, Regulation of immune responses by prostaglandin E2, J Immunol., 188, 21, 10.4049/jimmunol.1101029

Rocca, 2002, Cyclooxygenases and prostaglandins: shaping up the immune response, Int Immunopharmacol., 2, 603, 10.1016/S1567-5769(01)00204-1

Sreeramkumar, 2012, Prostaglandin E2 and T cells: friends or foes?, Immunol Cell Biol., 90, 579, 10.1038/icb.2011.75

Wu, 1998, Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E, Am J Physiol., 275, C661, 10.1152/ajpcell.1998.275.3.C661

Beharka, 2002, Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite, Free Radic Biol Med., 32, 503, 10.1016/S0891-5849(01)00817-6

Hayek, 1997, Vitamin E supplementation decreases lung virus titers in mice infected with influenza, J Infect Dis., 176, 273, 10.1086/517265

Han, 2000, Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus, Immunology, 100, 487, 10.1046/j.1365-2567.2000.00070.x

Bou, 2015, The alpha-tocopherol form of vitamin E reverses age-associated susceptibility to Streptococcus pneumoniae Lung infection by modulating pulmonary neutrophil recruitment, J Immunol., 194, 1090, 10.4049/jimmunol.1402401

Chavance, 1989, Vitamin status, immunity and infections in an elderly population, Eur J Clin Nutr., 43, 827

Meydani, 2004, Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial, JAMA, 292, 828, 10.1001/jama.292.7.828

Hemila, 2011, Subgroup analysis of large trials can guide further research: a case study of vitamin E and pneumonia, Clin Epidemiol., 3, 51, 10.2147/CLEP.S16114

Hemila, 2004, Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers, Chest, 125, 557, 10.1378/chest.125.2.557

Hemila, 2006, The effect of vitamin E on common cold incidence is modified by age, smoking and residential neighborhood, J Am Coll Nutr., 25, 332, 10.1080/07315724.2006.10719543

Graat, 2002, Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial, JAMA, 288, 715, 10.1001/jama.288.6.715

Prasad, 2013, Discovery of human zinc deficiency: its impact on human health and disease, Adv Nutr., 4, 176, 10.3945/an.112.003210

Wessels, 2017, Zinc as a gatekeeper of immune function, Nutrients, 9, E1286, 10.3390/nu9121286

Gammoh, 2017, Zinc in infection and inflammation, Nutrients, 9, E624, 10.3390/nu9060624

Maywald, 2017, Zinc signals and immunity, Int J Mol Sci, 18, E2222, 10.3390/ijms18102222

Caulfield, 2004, Zinc Deficiency, 257

Wessells, 2012, Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting, PLoS ONE, 7, e50568, 10.1371/journal.pone.0050568

Prasad, 1993, Zinc deficiency in elderly patients, Nutrition, 9, 218

Sandstead, 1982, Zinc nutriture in the elderly in relation to taste acuity, immune response, and wound healing, Am J Clin Nutr., 36, 1046, 10.1093/ajcn/36.5.1046

Mocchegiani, 2004, NK and NKT cell functions in immunosenescence, Aging Cell, 3, 177, 10.1111/j.1474-9728.2004.00107.x

Haase, 2009, The immune system and the impact of zinc during aging, Immun Ageing, 6, 9, 10.1186/1742-4933-6-9

Keen, 1990, Zinc deficiency and immune function, Annu Rev Nutr., 10, 415, 10.1146/annurev.nu.10.070190.002215

Mitchell, 2006, Thymic output, ageing and zinc, Biogerontology, 7, 461, 10.1007/s10522-006-9061-7

Prasad, 2000, Effects of zinc deficiency on Th1 and Th2 cytokine shifts, J Infect Dis., 182, S62, 10.1086/315916

Prasad, 2008, Zinc in human health: effect of zinc on immune cells, Mol Med., 14, 353, 10.2119/2008-00033.Prasad

Fischer, 2004, Zinc and the risk for infectious disease, Annu Rev Nutr., 24, 255, 10.1146/annurev.nutr.23.011702.073054

Rosenkranz, 2016, Induction of regulatory T cells in Th1-/Th17-driven experimental autoimmune encephalomyelitis by zinc administration, J Nutr Biochem., 29, 116, 10.1016/j.jnutbio.2015.11.010

Rosenkranz, 2016, Zinc supplementation induces regulatory T cells by inhibition of Sirt-1 deacetylase in mixed lymphocyte cultures, Mol Nutr Food Res., 60, 661, 10.1002/mnfr.201500524

Kitabayashi, 2010, Zinc suppresses Th17 development via inhibition of STAT3 activation, Int Immunol., 22, 375, 10.1093/intimm/dxq017

Maywald, 2018, Zinc supplementation plays a crucial role in T helper 9 differentiation in allogeneic immune reactions and non-activated T cells, J Trace Elem Med Biol., 50, 482, 10.1016/j.jtemb.2018.02.004

George, 2016, Zinc induces dendritic cell tolerogenic phenotype and skews regulatory T Cell-Th17 balance, J Immunol., 197, 1864, 10.4049/jimmunol.1600410

Dardenne, 1993, Restoration of the thymus in aging mice by in vivo zinc supplementation, Clin Immunol Immunopathol., 66, 127, 10.1006/clin.1993.1016

Mocchegiani, 1995, Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice, Int J Immunopharmacol., 17, 703, 10.1016/0192-0561(95)00059-B

Wong, 2009, Zinc supplementation increases zinc status and thymopoiesis in aged mice, J Nutr., 139, 1393, 10.3945/jn.109.106021

Iovino, 2018, High-dose zinc oral supplementation after stem cell transplantation causes an increase of TRECs and CD4+ naive lymphocytes and prevents TTV reactivation, Leuk Res., 70, 20, 10.1016/j.leukres.2018.04.016

Fortes, 1998, The effect of zinc and vitamin A supplementation on immune response in an older population, J Am Geriatr Soc., 46, 19, 10.1111/j.1532-5415.1998.tb01008.x

Kahmann, 2006, Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals, Biogerontology, 7, 429, 10.1007/s10522-006-9058-2

Dardenne, 1982, Contribution of zinc and other metals to the biological activity of the serum thymic factor, Proc Natl Acad Sci USA., 79, 5370, 10.1073/pnas.79.17.5370

Bach, 1972, Evidence for a serum-factor secreted by the human thymus, Lancet, 2, 1056, 10.1016/S0140-6736(72)92339-2

Iwata, 1979, Circulating thymic hormone levels in zinc deficiency, Cell Immunol., 47, 100, 10.1016/0008-8749(79)90318-6

Boukaiba, 1993, A physiological amount of zinc supplementation: effects on nutritional, lipid, and thymic status in an elderly population, Am J Clin Nutr., 57, 566, 10.1093/ajcn/57.4.566

Mocchegiani, 2003, Metallothioneins/PARP-1/IL-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply, Mech Ageing Dev., 124, 459, 10.1016/S0047-6374(03)00023-X

Ravaglia, 2000, Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/ = 90 y, Am J Clin Nutr., 71, 590, 10.1093/ajcn/71.2.590

Mocchegiani, 2008, Zinc deficiency and IL-6−174G/C polymorphism in old people from different European countries: effect of zinc supplementation, . Exp Gerontol., 43, 433, 10.1016/j.exger.2008.01.001

Muzzioli, 1992, In vitro restoration by thymulin of NK activity of cells from old mice, Int J Immunopharmacol., 14, 57, 10.1016/0192-0561(92)90105-T

Cossack, 1989, T-lymphocyte dysfunction in the elderly associated with zinc deficiency and subnormal nucleoside phosphorylase activity: effect of zinc supplementation, Eur J Cancer Clin Oncol., 25, 973, 10.1016/0277-5379(89)90156-9

Duchateau, 1981, Beneficial effects of oral zinc supplementation on the immune response of old people, Am J Med., 70, 1001, 10.1016/0002-9343(81)90849-4

Wagner, 1983, Zinc nutriture and cell-mediated immunity in the aged, Int J Vitam Nutr Res., 53, 94

Prasad, 2006, Correction of interleukin-2 gene expression by in vitro zinc addition to mononuclear cells from zinc-deficient human subjects: a specific test for zinc deficiency in humans, Transl Res., 148, 325, 10.1016/j.trsl.2006.07.008

Bao, 2011, Intracellular free zinc up-regulates IFN-gamma and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells, Biochem Biophys Res Commun., 407, 703, 10.1016/j.bbrc.2011.03.084

Barnett, 2016, Effect of zinc supplementation on serum zinc concentration and T cell proliferation in nursing home elderly: a randomized, double-blind, placebo-controlled trial, Am J Clin Nutr., 103, 942, 10.3945/ajcn.115.115188

Gibson, 1998, Assessment of dietary zinc in a population, Am J Clin Nutr., 68, 430S, 10.1093/ajcn/68.2.430S

Yakoob, 2011, Preventive zinc supplementation in developing countries: impact on mortality and morbidity due to diarrhea, pneumonia and malaria, BMC Public Health, 11, S23, 10.1186/1471-2458-11-S3-S23

Ruel, 1997, Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children, Pediatrics, 99, 808, 10.1542/peds.99.6.808

Brooks, 2005, Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial, Lancet, 366, 999, 10.1016/S0140-6736(05)67109-7

Bao, 2008, Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients, Transl Res., 152, 67, 10.1016/j.trsl.2008.06.001

Girodon, 1997, Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial, Ann Nutr Metab., 41, 98, 10.1159/000177984

Prasad, 2007, Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress, Am J Clin Nutr., 85, 837, 10.1093/ajcn/85.3.837

Meydani, 2007, Serum zinc and pneumonia in nursing home elderly, Am J Clin Nutr., 86, 1167, 10.1093/ajcn/86.4.1167

Williams, 1988, Iron and zinc status in multiple sclerosis patients with pressure sores, Eur J Clin Nutr., 42, 321

Dore-Duffy, 1990, Zinc profiles in rheumatoid arthritis, Clin Exp Rheumatol., 8, 541

Bideci, 2005, Serum zinc, insulin-like growth factor-I and insulin-like growth factor binding protein-3 levels in children with type 1 diabetes mellitus, J Pediatr Endocrinol Metab., 18, 1007, 10.1515/JPEM.2005.18.10.1007

Sanna, 2018, Zinc status and autoimmunity: a systematic review and meta-analysis, Nutrients, 10, E68, 10.3390/nu10010068

Souffriau, 2018, Mechanistic insights into the protective impact of zinc on sepsis, Cytokine Growth Factor Rev., 39, 92, 10.1016/j.cytogfr.2017.12.002

Ganatra, 2017, Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis, Innate Immun., 23, 67, 10.1177/1753425916677073

Wessels, 2015, Zinc dyshomeostasis during polymicrobial sepsis in mice involves zinc transporter Zip14 and can be overcome by zinc supplementation, Am J Physiol Gastrointest Liver Physiol., 309, G768, 10.1152/ajpgi.00179.2015

Banupriya, 2018, Short term oral zinc supplementation among babies with neonatal sepsis for reducing mortality and improving outcome - A double-blind randomized controlled trial, Indian J Pediatr., 85, 5, 10.1007/s12098-017-2444-8

Banupriya, 2017, Efficacy of zinc supplementation on serum calprotectin, inflammatory cytokines and outcome in neonatal sepsis - a randomized controlled trial, J Matern Fetal Neonatal Med., 30, 1627, 10.1080/14767058.2016.1220524

Alker, 2018, Zinc and sepsis, Nutrients, 10, 976, 10.3390/nu10080976

Calder, 2017, Omega-3 fatty acids and inflammatory processes: from molecules to man, Biochem Soc Trans., 45, 1105, 10.1042/BST20160474

Fritsche, 2006, Fatty acids as modulators of the immune response, Annu Rev Nutr., 26, 45, 10.1146/annurev.nutr.25.050304.092610

Galli, 2009, Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review, Ann Nutr Metab., 55, 123, 10.1159/000228999

Kim, 2010, Regulatory activity of polyunsaturated fatty acids in T-cell signaling, Prog Lipid Res., 49, 250, 10.1016/j.plipres.2010.01.002

Shaikh, 2006, Polyunsaturated fatty acids, membrane organization, T cells, and antigen presentation, Am J Clin Nutr., 84, 1277, 10.1093/ajcn/84.6.1277

Whelan, 2016, N-3 polyunsaturated fatty acids modulate B cell activity in pre-clinical models: implications for the immune response to infections, Eur J Pharmacol., 785, 10, 10.1016/j.ejphar.2015.03.100

Zhao, 2004, Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation, J Am Coll Nutr., 23, 71, 10.1080/07315724.2004.10719345

Mullen, 2010, Anti-inflammatory effects of EPA and DHA are dependent upon time and dose-response elements associated with LPS stimulation in THP-1-derived macrophages, J Nutr Biochem., 21, 444, 10.1016/j.jnutbio.2009.02.008

Serhan, 2014, Pro-resolving lipid mediators are leads for resolution physiology, Nature, 510, 92, 10.1038/nature13479

Serhan, 2008, Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators, Nat Rev Immunol., 8, 349, 10.1038/nri2294

Schwab, 2007, Resolvin E1 and protectin D1 activate inflammation-resolution programmes, Nature, 447, 869, 10.1038/nature05877

Hong, 2003, Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation, J Biol Chem., 278, 14677, 10.1074/jbc.M300218200

Arita, 2005, Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis, Proc Natl Acad Sci USA., 102, 7671, 10.1073/pnas.0409271102

Weylandt, 2007, Lipoxins and resolvins in inflammatory bowel disease, Inflamm Bowel Dis., 13, 797, 10.1002/ibd.20109

Marcon, 2013, Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis, J Immunol., 191, 4288, 10.4049/jimmunol.1202743

Fan, 2004, Dietary docosahexaenoic acid suppresses T cell protein kinase C theta lipid raft recruitment and IL-2 production, J Immunol., 173, 6151, 10.4049/jimmunol.173.10.6151

Switzer, 2004, Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in Th1-polarized murine CD4+ T-cells, J Lipid Res., 45, 1482, 10.1194/jlr.M400028-JLR200

Pompos, 2002, Antigen-driven murine CD4+ T lymphocyte proliferation and interleukin-2 production are diminished by dietary (n-3) polyunsaturated fatty acids, J Nutr., 132, 3293, 10.1093/jn/132.11.3293

Meydani, 1993, Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment, J Clin Invest., 92, 105, 10.1172/JCI116537

Kim, 2008, n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation, J Immunol., 181, 6236, 10.4049/jimmunol.181.9.6236

Yog, 2010, n-3 polyunsaturated fatty acids suppress mitochondrial translocation to the immunologic synapse and modulate calcium signaling in T cells, J Immunol., 184, 5865, 10.4049/jimmunol.0904102

Fan, 2018, Remodelling of primary human CD4+ T cell plasma membrane order by n-3 PUFA, Br J Nutr., 119, 163, 10.1017/S0007114517003385

Hou, 2016, Omega-3 fatty acids, lipid rafts, and T cell signaling, Eur J Pharmacol., 785, 2, 10.1016/j.ejphar.2015.03.091

Miguel, 2011, Primary human CD4+ T cells have diverse levels of membrane lipid order that correlate with their function, J Immunol., 186, 3505, 10.4049/jimmunol.1002980

Shaikh, 2012, n-3 Polyunsaturated fatty acids exert immunomodulatory effects on lymphocytes by targeting plasma membrane molecular organization, Mol Aspects Med., 33, 46, 10.1016/j.mam.2011.10.002

Kim, 2014, Dietary fish oil and DHA down-regulate antigen-activated CD4+ T-cells while promoting the formation of liquid-ordered mesodomains, Br J Nutr., 111, 254, 10.1017/S0007114513002444

Monk, 2013, n3 PUFAs reduce mouse CD4+ T-cell ex vivo polarization into Th17 cells, J Nutr., 143, 1501, 10.3945/jn.113.178178

Monk, 2012, Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis, PLoS ONE, 7, e49739, 10.1371/journal.pone.0049739

Zhang, 2005, Dietary (n-3) polyunsaturated fatty acids modulate murine Th1/Th2 balance toward the Th2 pole by suppression of Th1 development, J Nutr., 135, 1745, 10.1093/jn/135.7.1745

Bi, 2017, omega-3 polyunsaturated fatty acids ameliorate type 1 diabetes and autoimmunity, J Clin Invest., 127, 1757, 10.1172/JCI87388

Fujikawa, 1992, Eicosapentaenoic acid inhibits antigen-presenting cell function of murine splenocytes, Immunology, 75, 330

Hughes, 1996, Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes, Am J Clin Nutr., 63, 267, 10.1093/ajcn/63.2.267

Hughes, 1996, (n-3) Polyunsaturated fatty acids modulate the expression of functionally associated molecules on human monocytes in vitro, J Nutr., 126, 603, 10.1093/jn/126.3.603

Sanderson, 1997, Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells, J Leukoc Biol., 62, 771, 10.1002/jlb.62.6.771

Zapata-Gonzalez, 2008, Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR(gamma):RXR heterodimers: comparison with other polyunsaturated fatty acids, J Leukoc Biol., 84, 1172, 10.1189/jlb.1007688

Teague, 2013, Dendritic cell activation, phagocytosis and CD69 expression on cognate T cells are suppressed by n-3 long-chain polyunsaturated fatty acids, Immunology, 139, 386, 10.1111/imm.12088

Rockett, 2013, Fish oil disrupts MHC class II lateral organization on the B-cell side of the immunological synapse independent of B-T cell adhesion, J Nutr Biochem., 24, 1810, 10.1016/j.jnutbio.2013.02.013

Rockett, 2012, Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function, J Lipid Res., 53, 674, 10.1194/jlr.M021782

Gurzell, 2015, Marine fish oils are not equivalent with respect to B-cell membrane organization and activation, J Nutr Biochem., 26, 369, 10.1016/j.jnutbio.2014.11.005

Gurzell, 2013, DHA-enriched fish oil targets B cell lipid microdomains and enhances ex vivo and in vivo B cell function, J Leukoc Biol., 93, 463, 10.1189/jlb.0812394

Teague, 2014, Eicosapentaenoic and docosahexaenoic acid ethyl esters differentially enhance B-cell activity in murine obesity, J Lipid Res., 55, 1420, 10.1194/jlr.M049809

Calder, 2015, Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance, Biochim Biophys Acta, 1851, 469, 10.1016/j.bbalip.2014.08.010

Calder, 2009, Fatty acids and immune function: relevance to inflammatory bowel diseases, Int Rev Immunol., 28, 506, 10.3109/08830180903197480

Fernandes, 2008, Effects of n-3 fatty acids on autoimmunity and osteoporosis, Front Biosci., 13, 4015, 10.2741/2989

Miles, 2012, Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis, Br J Nutr., 107, S171, 10.1017/S0007114512001560

Hudert, 2006, Transgenic mice rich in endogenous omega-3 fatty acids are protected from colitis, Proc Natl Acad Sci USA., 103, 11276, 10.1073/pnas.0601280103

Ishida, 2010, Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis, Inflamm Bowel Dis., 16, 87, 10.1002/ibd.21029

Matsunaga, 2008, Omega-3 fatty acids exacerbate DSS-induced colitis through decreased adiponectin in colonic subepithelial myofibroblasts, Inflamm Bowel Dis., 14, 1348, 10.1002/ibd.20491

Woodworth, 2010, Dietary fish oil alters T lymphocyte cell populations and exacerbates disease in a mouse model of inflammatory colitis, Cancer Res., 70, 7960, 10.1158/0008-5472.CAN-10-1396

Belluzzi, 1996, Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease, N Engl J Med., 334, 1557, 10.1056/NEJM199606133342401

Seidner, 2005, An oral supplement enriched with fish oil, soluble fiber, and antioxidants for corticosteroid sparing in ulcerative colitis: a randomized, controlled trial, Clin Gastroenterol Hepatol., 3, 358, 10.1016/S1542-3565(04)00672-X

Lev-Tzion, 2014, Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease, Cochrane Database Syst Rev., 10.1002/14651858.CD006320.pub4

Turner, 2011, Maintenance of remission in inflammatory bowel disease using omega-3 fatty acids (fish oil): a systematic review and meta-analyses, Inflamm Bowel Dis., 17, 336, 10.1002/ibd.21374

Arm, 1988, Effect of dietary supplementation with fish oil lipids on mild asthma, Thorax, 43, 84, 10.1136/thx.43.2.84

Broughton, 1997, Reduced asthma symptoms with n-3 fatty acid ingestion are related to 5-series leukotriene production, Am J Clin Nutr., 65, 1011, 10.1093/ajcn/65.4.1011

Surette, 2008, The impact of a medical food containing gammalinolenic and eicosapentaenoic acids on asthma management and the quality of life of adult asthma patients, Curr Med Res Opin., 24, 559, 10.1185/030079908X273011

Hodge, 1998, Effect of dietary intake of omega-3 and omega-6 fatty acids on severity of asthma in children, Eur Respir J., 11, 361, 10.1183/09031936.98.11020361

Schubert, 2009, Effect of n-3 polyunsaturated fatty acids in asthma after low-dose allergen challenge, Int Arch Allergy Immunol., 148, 321, 10.1159/000170386

Kumar, 2016, n-3 Fatty acids and asthma, Nutr Res Rev., 29, 1, 10.1017/S0954422415000116

Anandan, 2009, Omega 3 and 6 oils for primary prevention of allergic disease: systematic review and meta-analysis, Allergy, 64, 840, 10.1111/j.1398-9995.2009.02042.x

Schachter, 2004, Health effects of omega-3 fatty acids on asthma, Evidence Reports/Technology Assessments, No. 91, 1

Goldberg, 2007, A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain, Pain, 129, 210, 10.1016/j.pain.2007.01.020

Gioxari, 2018, Intake of omega-3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a systematic review and meta-analysis, Nutrition, 45, 114, 10.1016/j.nut.2017.06.023

Norris, 2007, Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes, JAMA, 298, 1420, 10.1001/jama.298.12.1420

Stene, 2003, Use of cod liver oil during the first year of life is associated with lower risk of childhood-onset type 1 diabetes: a large, population-based, case-control study, Am J Clin Nutr., 78, 1128, 10.1093/ajcn/78.6.1128

2001, Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powerder Milk and Live Lactic Acid Bacteria. Food and Agriculture Organization of the United Nations and World Health Organization Expert Consultation Report, 1

Hill, 2014, Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic, Nat Rev Gastroenterol Hepatol., 11, 506, 10.1038/nrgastro.2014.66

Galdeano, 2004, Role of viability of probiotic strains in their persistence in the gut and in mucosal immune stimulation, J Appl Microbiol., 97, 673, 10.1111/j.1365-2672.2004.02353.x

Thomas, 2010, Probiotics-host communication: modulation of signaling pathways in the intestine, Gut Microbes, 1, 1, 10.4161/gmic.1.3.11712

Macpherson, 2004, Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria, Science, 303, 1662, 10.1126/science.1091334

Muscettola, 1994, Effects of lactobacilli on interferon production in young and aged mice, Ann N Y Acad Sci., 717, 226, 10.1111/j.1749-6632.1994.tb12092.x

Baba, 2009, Selected commensal-related bacteria and Toll-like receptor 3 agonist combinatorial codes synergistically induce interleukin-12 production by dendritic cells to trigger a T helper type 1 polarizing programme, Immunology, 128, e523, 10.1111/j.1365-2567.2008.03022.x

Rescigno, 2001, Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria, Nat Immunol., 2, 361, 10.1038/86373

Vientos-Plotts, 2017, Oral probiotics alter healthy feline respiratory microbiota, Front Microbiol., 8, 1287, 10.3389/fmicb.2017.01287

Davidson, 2011, Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial, Eur J Clin Nutr., 65, 501, 10.1038/ejcn.2010.289

Elmadfa, 2010, Immune-stimulating effects of lactic acid bacteria in vivo and in vitro, Proc Nutr Soc., 69, 416, 10.1017/S0029665110001710

Vidal, 2008, Effect of Lactobacillus paracasei NCC2461 on antigen-specific T-cell mediated immune responses in aged mice, Rejuvenation Res., 11, 957, 10.1089/rej.2008.0780

Borchers, 2002, The influence of yogurt/Lactobacillus on the innate and acquired immune response, Clin Rev Allergy Immunol., 22, 207, 10.1007/s12016-002-0009-7

Delcenserie, 2008, Immunomodulatory effects of probiotics in the intestinal tract, Curr Issues Mol Biol., 10, 37

Arunachalam, 2000, Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019), Eur J Clin Nutr., 54, 263, 10.1038/sj.ejcn.1600938

Kekkonen, 2008, Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults, World J Gastroenterol., 14, 2029, 10.3748/wjg.14.2029

Spanhaak, 1998, The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans, Eur J Clin Nutr., 52, 899, 10.1038/sj.ejcn.1600663

Koch, 2012, The life and death of epithelia during inflammation: lessons learned from the gut, Annu Rev Pathol., 7, 35, 10.1146/annurev-pathol-011811-120905

Kang, 2015, Probiotics as an immune modulator, J Nutr Sci Vitaminol., 61, S103, 10.3177/jnsv.61.S103

Tobita, 2010, Lactobacillus crispatus KT-11 enhances intestinal immune functions in C3H/HeN mice, J Nutr Sci Vitaminol., 56, 441, 10.3177/jnsv.56.441

Ya, 2008, Immunological evaluation of Lactobacillus casei Zhang: a newly isolated strain from koumiss in Inner Mongolia, China, BMC Immunol., 68

Yang, 2009, Oral administration of live Bifidobacterium substrains isolated from healthy centenarians enhanced immune function in BALB/c mice, Nutr Res., 29, 281, 10.1016/j.nutres.2009.03.010

Lee, 2005, Enhancement in ex vivo phagocytic capacity of peritoneal leukocytes in mice by oral delivery of various lactic-acid-producing bacteria, Curr Microbiol., 50, 24, 10.1007/s00284-004-4377-5

Tsai, 2008, Time-dependent persistence of enhanced immune response by a potential probiotic strain Lactobacillus paracasei subsp. paracasei NTU 101, Int J Food Microbiol., 128, 219, 10.1016/j.ijfoodmicro.2008.08.009

Gill, 2001, Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes, J Clin Immunol., 21, 264, 10.1023/A:1010979225018

Sheih, 2001, Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001, J Am Coll Nutr., 20, 149, 10.1080/07315724.2001.10719027

Parra, 2004, Daily ingestion of fermented milk containing Lactobacillus casei DN114001 improves innate-defense capacity in healthy middle-aged people, J Physiol Biochem., 60, 85, 10.1007/BF03168444

Fang, 2000, Modulation of humoral immune response through probiotic intake, FEMS Immunol Med Microbiol., 29, 47, 10.1111/j.1574-695X.2000.tb01504.x

Pelto, 1998, Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immunostimulatory effect in healthy subjects, Clin Exp Allergy, 28, 1474, 10.1046/j.1365-2222.1998.00449.x

Barberi, 2015, T cell polarizing properties of probiotic bacteria, Immunol Lett., 168, 337, 10.1016/j.imlet.2015.11.005

Dwivedi, 2016, Induction of regulatory T cells: a role for probiotics and prebiotics to suppress autoimmunity, Autoimmun Rev., 15, 379, 10.1016/j.autrev.2016.01.002

Fu, 2010, Effects of Bifidobacterium bifidum on adaptive immune senescence in aging mice, Microbiol Immunol., 54, 578, 10.1111/j.1348-0421.2010.00255.x

Goodwin, 2006, Antibody response to influenza vaccination in the elderly: a quantitative review, Vaccine, 24, 1159, 10.1016/j.vaccine.2005.08.105

Boge, 2009, A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials, Vaccine, 27, 5677, 10.1016/j.vaccine.2009.06.094

Fukushima, 2007, Improvement of nutritional status and incidence of infection in hospitalised, enterally fed elderly by feeding of fermented milk containing probiotic Lactobacillus johnsonii La1 (NCC533), Br J Nutr., 98, 969, 10.1017/S0007114507764723

Guillemard, 2010, Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial, Br J Nutr., 103, 58, 10.1017/S0007114509991395

Turchet, 2003, Effect of fermented milk containing the probiotic Lactobacillus casei DN-114001 on winter infections in free-living elderly subjects: a randomised, controlled pilot study, J Nutr Health Aging, 75

Makino, 2010, Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, Br J Nutr., 104, 998, 10.1017/S000711451000173X

Mane, 2011, A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-controlled, randomized pilot trial, Nutr Hosp., 26, 228

Ivory, 2008, Oral delivery of Lactobacillus casei Shirota modifies allergen-induced immune responses in allergic rhinitis, Clin Exp Allergy, 38, 1282, 10.1111/j.1365-2222.2008.03025.x

Ivory, 2013, Oral delivery of a probiotic induced changes at the nasal mucosa of seasonal allergic rhinitis subjects after local allergen challenge: a randomised clinical trial, PLoS ONE, 8, e78650, 10.1371/journal.pone.0078650

Ghadimi, 2008, Effects of probiotic bacteria and their genomic DNA on TH1/TH2-cytokine production by peripheral blood mononuclear cells (PBMCs) of healthy and allergic subjects, Immunobiology, 213, 677, 10.1016/j.imbio.2008.02.001

Pae, 2013, Immunomodulating effects of epigallocatechin-3-gallate from green tea: mechanisms and applications, Food Funct., 4, 1287, 10.1039/c3fo60076a

Dona, 2003, Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis, J Immunol., 170, 4335, 10.4049/jimmunol.170.8.4335

Takano, 2004, Inhibitory effect of (-)-epigallocatechin 3-gallate, a polyphenol of green tea, on neutrophil chemotaxis in vitro and in vivo, J Agric Food Chem., 52, 4571, 10.1021/jf0355194

Chan, 2012, Inhibitory effect of Chinese green tea on cigarette smoke-induced up-regulation of airway neutrophil elastase and matrix metalloproteinase-12 via antioxidant activity, Free Radic Res., 46, 1123, 10.3109/10715762.2012.692786

Melgarejo, 2009, Epigallocatechin gallate reduces human monocyte mobility and adhesion in vitro, Br J Pharmacol., 158, 1705, 10.1111/j.1476-5381.2009.00452.x

Murakami, 2003, Combinatorial effects of nonsteroidal anti-inflammatory drugs and food constituents on production of prostaglandin E2 and tumor necrosis factor-alpha in RAW264.7 murine macrophages, Biosci Biotechnol Biochem., 67, 1056, 10.1271/bbb.67.1056

Park, 2001, Involvement of ERK and protein tyrosine phosphatase signaling pathways in EGCG-induced cyclooxygenase-2 expression in Raw 264.7 cells, Biochem Biophys Res Commun., 286, 721, 10.1006/bbrc.2001.5415

Matsunaga, 2001, Legionella pneumophila replication in macrophages inhibited by selective immunomodulatory effects on cytokine formation by epigallocatechin gallate, a major form of tea catechins, Infect Immun., 69, 3947, 10.1128/IAI.69.6.3947-3953.2001

Pae, 2012, Dietary supplementation with high dose of epigallocatechin-3-gallate promotes inflammatory response in mice, J Nutr Biochem., 23, 526, 10.1016/j.jnutbio.2011.02.006

Ahn, 2004, Epigallocatechin-3-gallate, constituent of green tea, suppresses the LPS-induced phenotypic and functional maturation of murine dendritic cells through inhibition of mitogen-activated protein kinases and NF-kappaB, Biochem Biophys Res Commun., 313, 148, 10.1016/j.bbrc.2003.11.108

Yoneyama, 2008, Epigallocatechin gallate affects human dendritic cell differentiation and maturation, J Allergy Clin Immunol., 121, 209, 10.1016/j.jaci.2007.08.026

Hu, 1992, Mitogenic activity of (-)epigallocatechin gallate on B-cells and investigation of its structure-function relationship, Int J Immunopharmacol., 14, 1399, 10.1016/0192-0561(92)90011-9

Liu, 2012, Pro-apoptotic effect of epigallo-catechin-3-gallate on B lymphocytes through regulating BAFF/PI3K/Akt/mTOR signaling in rats with collagen-induced arthritis, Eur J Pharmacol., 690, 214, 10.1016/j.ejphar.2012.06.026

Wu, 2009, Green tea EGCG suppresses T cell proliferation through impairment of IL-2/IL-2 receptor signaling, Free Radic Biol Med., 47, 636, 10.1016/j.freeradbiomed.2009.06.001

Pae, 2010, Epigallocatechin-3-gallate directly suppresses T cell proliferation through impaired IL-2 utilization and cell cycle progression, J Nutr., 140, 1509, 10.3945/jn.110.124743

Kim, 2007, Tea polyphenol inhibits allostimulation in mixed lymphocyte culture, Cell Transplant., 16, 75, 10.3727/000000007783464515

Watson, 2005, Immune cell activation and subsequent epithelial dysfunction by Staphylococcus enterotoxin B is attenuated by the green tea polyphenol (-)-epigallocatechin gallate, Cell Immunol., 237, 7, 10.1016/j.cellimm.2005.08.030

Wang, 2013, Green tea epigallocatechin-3-gallate modulates differentiation of naive CD4(+) T cells into specific lineage effector cells, J Mol Med., 91, 485, 10.1007/s00109-012-0964-2

Wu, 2009, Naturally occurring flavonoids attenuate high glucose-induced expression of proinflammatory cytokines in human monocytic THP-1 cells, Mol Nutr Food Res., 53, 984, 10.1002/mnfr.200800495

Lyu, 2005, Production of cytokine and NO by RAW 264, . Arch Pharm Res., 28, 573, 10.1007/BF02977761

Wang, 2012, Epigallocatechin-3-gallate inhibits expression of receptors for T cell regulatory cytokines and their downstream signaling in mouse CD4+ T cells, J Nutr., 142, 566, 10.3945/jn.111.154419

Shim, 2008, (-)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in leukemia through the inhibition of ZAP-70 kinase, J Biol Chem., 283, 28370, 10.1074/jbc.M802200200

Nam, 2001, Ester bond-containing tea polyphenols potently inhibit proteasome activity in vitro and in vivo, J Biol Chem., 276, 13322, 10.1074/jbc.M004209200

Wu, 2012, Green tea EGCG, T cells, and T cell-mediated autoimmune diseases, Mol Aspects Med., 33, 107, 10.1016/j.mam.2011.10.001