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Vitamin A and the Immune System

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Nutrition and Immunity

Abstract

Vitamin A (retinol) is a lipid-soluble vitamin essential to multiple biological processes such as vision, reproduction, embryogenesis, and development of the nervous system. Retinoic acid (RA), the biologically active form of vitamin A, plays a crucial role in the development and regulation of the immune system. Recent evidence indicates that RA influences the functions of various populations of cells of innate and adaptive immune system. Vitamin A deficiency (VAD) has been shown to confer defects in both innate and adaptive immune compartments, and therefore impair immunity against pathogens. RA contributes to immune tolerance by suppressing effector T cell responses, which result in inhibition of tissue inflammation in autoimmune diseases. Moreover, RA can cause gut tropism by inducing the expression of gut-tropic integrins on T cells. This chapter discusses the effect of RA on the immune system in infectious and autoimmune diseases. Also, how RA affects the interplay between effector and regulatory T cells is addressed.

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References

  1. Villamor E, Fawzi WW. Effects of vitamin a supplementation on immune responses and correlation with clinical outcomes. Clin Microbiol Rev. 2005;18(3):446–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Harrison EH, Hussain MM. Mechanisms involved in the intestinal digestion and absorption of dietary vitamin A. J Nutr. 2001;131(5):1405–8.

    Article  CAS  PubMed  Google Scholar 

  3. Blomhoff R, Blomhoff HK. Overview of retinoid metabolism and function. J Neurobiol. 2006;66(7):606–30.

    Article  CAS  PubMed  Google Scholar 

  4. McDonald KG, Leach MR, Brooke KW, Wang C, Wheeler LW, Hanly EK, et al. Epithelial expression of the cytosolic retinoid chaperone cellular retinol binding protein II is essential for in vivo imprinting of local gut dendritic cells by lumenal retinoids. Am J Pathol. 2012;180(3):984–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kanai M, Raz A, Goodman DS. Retinol-binding protein: the transport protein for vitamin A in human plasma. J Clin Invest. 1968;47(9):2025–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Derebe MG, Zlatkov CM, Gattu S, Ruhn KA, Vaishnava S, Diehl GE, et al. Serum amyloid A is a retinol binding protein that transports retinol during bacterial infection. elife. 2014;3:e03206.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kawaguchi R, Yu J, Honda J, Hu J, Whitelegge J, Ping P, et al. A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A. Science. 2007;315(5813):820–5.

    Article  CAS  PubMed  Google Scholar 

  8. Duester G, Mic FA, Molotkov A. Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid. Chem Biol Interact. 2003;143–144:201–10.

    Article  PubMed  CAS  Google Scholar 

  9. Kumar S, Sandell LL, Trainor PA, Koentgen F, Duester G. Alcohol and aldehyde dehydrogenases: retinoid metabolic effects in mouse knockout models. Biochim Biophys Acta. 2012;1821(1):198–205.

    Article  CAS  PubMed  Google Scholar 

  10. Dolle P, Ruberte E, Kastner P, Petkovich M, Stoner CM, Gudas LJ, et al. Differential expression of genes encoding alpha, beta and gamma retinoic acid receptors and CRABP in the developing limbs of the mouse. Nature. 1989;342(6250):702–5.

    Article  CAS  PubMed  Google Scholar 

  11. Heyman RA, Mangelsdorf DJ, Dyck JA, Stein RB, Eichele G, Evans RM, et al. 9-cis retinoic acid is a high affinity ligand for the retinoid X receptor. Cell. 1992;68(2):397–406.

    Article  CAS  PubMed  Google Scholar 

  12. Kam RK, Deng Y, Chen Y, Zhao H. Retinoic acid synthesis and functions in early embryonic development. Cell Biosci. 2012;2(1):11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Nagy L, Schwabe JW. Mechanism of the nuclear receptor molecular switch. Trends Biochem Sci. 2004;29(6):317–24.

    Article  CAS  PubMed  Google Scholar 

  14. Thatcher JE, Isoherranen N. The role of CYP26 enzymes in retinoic acid clearance. Expert Opin Drug Metab Toxicol. 2009;5(8):875–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. MacLean G, Abu-Abed S, Dolle P, Tahayato A, Chambon P, Petkovich M. Cloning of a novel retinoic-acid metabolizing cytochrome P450, Cyp26B1, and comparative expression analysis with Cyp26A1 during early murine development. Mech Dev. 2001;107(1–2):195–201.

    Article  CAS  PubMed  Google Scholar 

  16. Majumdar A, Petrescu AD, Xiong Y, Noy N. Nuclear translocation of cellular retinoic acid-binding protein II is regulated by retinoic acid-controlled SUMOylation. J Biol Chem. 2011;286(49):42749–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schug TT, Berry DC, Shaw NS, Travis SN, Noy N. Opposing effects of retinoic acid on cell growth result from alternate activation of two different nuclear receptors. Cell. 2007;129(4):723–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dong D, Ruuska SE, Levinthal DJ, Noy N. Distinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid. J Biol Chem. 1999;274(34):23695–8.

    Article  CAS  PubMed  Google Scholar 

  19. Summers JA, Harper AR, Feasley CL, Van-Der-Wel H, Byrum JN, Hermann M, et al. Identification of apolipoprotein A-I as a retinoic acid-binding protein in the eye. J Biol Chem. 2016;291(36):18991–9005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Belatik A, Hotchandani S, Bariyanga J, Tajmir-Riahi HA. Binding sites of retinol and retinoic acid with serum albumins. Eur J Med Chem. 2012;48:114–23.

    Article  CAS  PubMed  Google Scholar 

  21. Czarnewski P, Das S, Parigi SM, Villablanca EJ. Retinoic acid and its role in modulating intestinal innate immunity. Nutrients. 2017;9(1):E68.

    Article  PubMed  CAS  Google Scholar 

  22. Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40(1):128–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Uematsu S, Fujimoto K, Jang MH, Yang BG, Jung YJ, Nishiyama M, et al. Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5. Nat Immunol. 2008;9(7):769–76.

    Article  CAS  PubMed  Google Scholar 

  24. Manicassamy S, Ravindran R, Deng J, Oluoch H, Denning TL, Kasturi SP, et al. Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity. Nat Med. 2009;15(4):401–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yokota A, Takeuchi H, Maeda N, Ohoka Y, Kato C, Song SY, et al. GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity. Int Immunol. 2009;21(4):361–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Huang G, Wang Y, Chi H. Control of T cell fates and immune tolerance by p38alpha signaling in mucosal CD103+ dendritic cells. J Immunol. 2013;191(2):650–9.

    Article  CAS  PubMed  Google Scholar 

  27. Manicassamy S, Reizis B, Ravindran R, Nakaya H, Salazar-Gonzalez RM, Wang YC, et al. Activation of beta-catenin in dendritic cells regulates immunity versus tolerance in the intestine. Science. 2010;329(5993):849–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Na SY, Kang BY, Chung SW, Han SJ, Ma X, Trinchieri G, et al. Retinoids inhibit interleukin-12 production in macrophages through physical associations of retinoid X receptor and NFkappaB. J Biol Chem. 1999;274(12):7674–80.

    Article  CAS  PubMed  Google Scholar 

  29. Mehta K, McQueen T, Tucker S, Pandita R, Aggarwal BB. Inhibition by all-trans-retinoic acid of tumor necrosis factor and nitric oxide production by peritoneal macrophages. J Leukoc Biol. 1994;55(3):336–42.

    Article  CAS  PubMed  Google Scholar 

  30. Maun NA, Gaines P, Khanna-Gupta A, Zibello T, Enriquez L, Goldberg L, et al. G-CSF signaling can differentiate promyelocytes expressing a defective retinoic acid receptor: evidence for divergent pathways regulating neutrophil differentiation. Blood. 2004;103(5):1693–701.

    Article  CAS  PubMed  Google Scholar 

  31. Higuchi H, Nagahata H. Effects of vitamins A and E on superoxide production and intracellular signaling of neutrophils in Holstein calves. Can J Vet Res. 2000;64(1):69–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Zhao Z, Ross AC. Retinoic acid repletion restores the number of leukocytes and their subsets and stimulates natural cytotoxicity in vitamin A-deficient rats. J Nutr. 1995;125(8):2064–73.

    Article  CAS  PubMed  Google Scholar 

  33. Klebanoff CA, Spencer SP, Torabi-Parizi P, Grainger JR, Roychoudhuri R, Ji Y, et al. Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J Exp Med. 2013;210(10):1961–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Beijer MR, Molenaar R, Goverse G, Mebius RE, Kraal G, den Haan JM. A crucial role for retinoic acid in the development of Notch-dependent murine splenic CD8- CD4- and CD4+ dendritic cells. Eur J Immunol. 2013;43(6):1608–16.

    Article  CAS  PubMed  Google Scholar 

  35. Beijer MR, Kraal G, den Haan JM. Vitamin A and dendritic cell differentiation. Immunology. 2014;142(1):39–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Radtke F, MacDonald HR, Tacchini-Cottier F. Regulation of innate and adaptive immunity by Notch. Nat Rev Immunol. 2013;13(6):427–37.

    Article  CAS  PubMed  Google Scholar 

  37. Zhu B, Buttrick T, Bassil R, Zhu C, Olah M, Wu C, et al. IL-4 and retinoic acid synergistically induce regulatory dendritic cells expressing Aldh1a2. J Immunol. 2013;191(6):3139–51.

    Article  CAS  PubMed  Google Scholar 

  38. DePaolo RW, Abadie V, Tang F, Fehlner-Peach H, Hall JA, Wang W, et al. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens. Nature. 2011;471(7337):220–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Geissmann F, Revy P, Brousse N, Lepelletier Y, Folli C, Durandy A, et al. Retinoids regulate survival and antigen presentation by immature dendritic cells. J Exp Med. 2003;198(4):623–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhan XX, Liu Y, Yang JF, Wang GY, Mu L, Zhang TS, et al. All-trans-retinoic acid ameliorates experimental allergic encephalomyelitis by affecting dendritic cell and monocyte development. Immunology. 2013;138(4):333–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Saurer L, McCullough KC, Summerfield A. In vitro induction of mucosa-type dendritic cells by all-trans retinoic acid. J Immunol. 2007;179(6):3504–14.

    Article  CAS  PubMed  Google Scholar 

  42. Darmanin S, Chen J, Zhao S, Cui H, Shirkoohi R, Kubo N, et al. All-trans retinoic acid enhances murine dendritic cell migration to draining lymph nodes via the balance of matrix metalloproteinases and their inhibitors. J Immunol. 2007;179(7):4616–25.

    Article  CAS  PubMed  Google Scholar 

  43. Sirisinha S. The pleiotropic role of vitamin A in regulating mucosal immunity. Asian Pac J Allergy Immunol. 2015;33(2):71–89.

    PubMed  Google Scholar 

  44. Stock A, Booth S, Cerundolo V. Prostaglandin E2 suppresses the differentiation of retinoic acid-producing dendritic cells in mice and humans. J Exp Med. 2011;208(4):761–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hurst RJ, Else KJ. The retinoic acid-producing capacity of gut dendritic cells and macrophages is reduced during persistent T. muris infection. Parasite Immunol. 2013;35(7–8):229–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Laffont S, Siddiqui KR, Powrie F. Intestinal inflammation abrogates the tolerogenic properties of MLN CD103+ dendritic cells. Eur J Immunol. 2010;40(7):1877–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Yang Y, Vacchio MS, Ashwell JD. 9-cis-retinoic acid inhibits activation-driven T-cell apoptosis: implications for retinoid X receptor involvement in thymocyte development. Proc Natl Acad Sci U S A. 1993;90(13):6170–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Garbe A, Buck J, Hammerling U. Retinoids are important cofactors in T cell activation. J Exp Med. 1992;176(1):109–17.

    Article  CAS  PubMed  Google Scholar 

  49. Peng SL, Gerth AJ, Ranger AM, Glimcher LH. NFATc1 and NFATc2 together control both T and B cell activation and differentiation. Immunity. 2001;14(1):13–20.

    Article  CAS  PubMed  Google Scholar 

  50. Hall JA, Cannons JL, Grainger JR, Dos Santos LM, Hand TW, Naik S, et al. Essential role for retinoic acid in the promotion of CD4(+) T cell effector responses via retinoic acid receptor alpha. Immunity. 2011;34(3):435–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dawson H, Solano-Aguilar G, Beal M, Beshah E, Vangimalla V, Jones E, et al. Localized Th1-, Th2-, T regulatory cell-, and inflammation-associated hepatic and pulmonary immune responses in Ascaris suum-infected swine are increased by retinoic acid. Infect Immun. 2009;77(6):2576–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, et al. The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity. 2009;30(6):832–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bono MR, Tejon G, Flores-Santibanez F, Fernandez D, Rosemblatt M, Sauma D. Retinoic acid as a modulator of T cell immunity. Nutrients. 2016;8(6):349.

    Article  PubMed Central  CAS  Google Scholar 

  54. Engedal N, Gjevik T, Blomhoff R, Blomhoff HK. All-trans retinoic acid stimulates IL-2-mediated proliferation of human T lymphocytes: early induction of cyclin D3. J Immunol. 2006;177(5):2851–61.

    Article  CAS  PubMed  Google Scholar 

  55. Zhang Y, Reynolds JM, Chang SH, Martin-Orozco N, Chung Y, Nurieva RI, et al. MKP-1 is necessary for T cell activation and function. J Biol Chem. 2009;284(45):30815–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bono MR, Elgueta R, Sauma D, Pino K, Osorio F, Michea P, et al. The essential role of chemokines in the selective regulation of lymphocyte homing. Cytokine Growth Factor Rev. 2007;18(1–2):33–43.

    Article  CAS  PubMed  Google Scholar 

  57. Raverdeau M, Mills KH. Modulation of T cell and innate immune responses by retinoic acid. J Immunol. 2014;192(7):2953–8.

    Article  CAS  PubMed  Google Scholar 

  58. Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY. Retinoic acid imprints gut-homing specificity on T cells. Immunity. 2004;21(4):527–38.

    Article  CAS  PubMed  Google Scholar 

  59. Liu ZM, Wang KP, Ma J, Guo Zheng S. The role of all-trans retinoic acid in the biology of Foxp3+ regulatory T cells. Cell Mol Immunol. 2015;12(5):553–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Nolting J, Daniel C, Reuter S, Stuelten C, Li P, Sucov H, et al. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines. J Exp Med. 2009;206(10):2131–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Takeuchi H, Yokota A, Ohoka Y, Iwata M. Cyp26b1 regulates retinoic acid-dependent signals in T cells and its expression is inhibited by transforming growth factor-beta. PLoS One. 2011;6(1):e16089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Xiao S, Jin H, Korn T, Liu SM, Oukka M, Lim B, et al. Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol. 2008;181(4):2277–84.

    Article  CAS  PubMed  Google Scholar 

  63. Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, et al. Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science. 2007;317(5835):256–60.

    Article  CAS  PubMed  Google Scholar 

  64. Coombes JL, Siddiqui KR, Arancibia-Carcamo CV, Hall J, Sun CM, Belkaid Y, et al. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med. 2007;204(8):1757–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Villablanca EJ. Retinoic acid-producing DCs and gut-tropic FOXP3(+) regulatory T cells in the induction of oral tolerance. Oncoimmunology. 2013;2(2):e22987.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Lu L, Lan Q, Li Z, Zhou X, Gu J, Li Q, et al. Critical role of all-trans retinoic acid in stabilizing human natural regulatory T cells under inflammatory conditions. Proc Natl Acad Sci U S A. 2014;111(33):E3432–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Takahashi H, Kanno T, Nakayamada S, Hirahara K, Sciume G, Muljo SA, et al. TGF-beta and retinoic acid induce the microRNA miR-10a, which targets Bcl-6 and constrains the plasticity of helper T cells. Nat Immunol. 2012;13(6):587–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bai A, Ma AG, Yong M, Weiss CR, Ma Y, Guan Q, et al. AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis. Biochem Pharmacol. 2010;80(11):1708–17.

    Article  CAS  PubMed  Google Scholar 

  69. Elias KM, Laurence A, Davidson TS, Stephens G, Kanno Y, Shevach EM, et al. Retinoic acid inhibits Th17 polarization and enhances FoxP3 expression through a Stat-3/Stat-5 independent signaling pathway. Blood. 2008;111(3):1013–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27:485–517.

    Article  CAS  PubMed  Google Scholar 

  71. Kang SG, Lim HW, Andrisani OM, Broxmeyer HE, Kim CH. Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. J Immunol. 2007;179(6):3724–33.

    Article  CAS  PubMed  Google Scholar 

  72. Cha HR, Chang SY, Chang JH, Kim JO, Yang JY, Kim CH, et al. Downregulation of Th17 cells in the small intestine by disruption of gut flora in the absence of retinoic acid. J Immunol. 2010;184(12):6799–806.

    Article  CAS  PubMed  Google Scholar 

  73. Rampal R, Awasthi A, Ahuja V. Retinoic acid-primed human dendritic cells inhibit Th9 cells and induce Th1/Th17 cell differentiation. J Leukoc Biol. 2016;100(1):111–20.

    Article  CAS  PubMed  Google Scholar 

  74. Cantorna MT, Nashold FE, Hayes CE. In vitamin A deficiency multiple mechanisms establish a regulatory T helper cell imbalance with excess Th1 and insufficient Th2 function. J Immunol. 1994;152(4):1515–22.

    CAS  PubMed  Google Scholar 

  75. Serafini N, Vosshenrich CA, Di Santo JP. Transcriptional regulation of innate lymphoid cell fate. Nat Rev Immunol. 2015;15(7):415–28.

    Article  CAS  PubMed  Google Scholar 

  76. Kim MH, Taparowsky EJ, Kim CH. Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut. Immunity. 2015;43(1):107–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Bernink JH, Krabbendam L, Germar K, de Jong E, Gronke K, Kofoed-Nielsen M, et al. Interleukin-12 and -23 control plasticity of CD127(+) group 1 and group 3 innate lymphoid cells in the intestinal lamina propria. Immunity. 2015;43(1):146–60.

    Article  CAS  PubMed  Google Scholar 

  78. Spencer SP, Wilhelm C, Yang Q, Hall JA, Bouladoux N, Boyd A, et al. Adaptation of innate lymphoid cells to a micronutrient deficiency promotes type 2 barrier immunity. Science. 2014;343(6169):432–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Trinchieri G. Biology of natural killer cells. Adv Immunol. 1989;47:187–376.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Cerwenka A, Bakker AB, McClanahan T, Wagner J, Wu J, Phillips JH, et al. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity. 2000;12(6):721–7.

    Article  CAS  PubMed  Google Scholar 

  81. Jinushi M, Takehara T, Tatsumi T, Kanto T, Groh V, Spies T, et al. Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. Int J Cancer. 2003;104(3):354–61.

    Article  CAS  PubMed  Google Scholar 

  82. Szatmari I, Pap A, Ruhl R, Ma JX, Illarionov PA, Besra GS, et al. PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006;203(10):2351–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009;31(2):331–41.

    Article  CAS  PubMed  Google Scholar 

  84. Mielke LA, Jones SA, Raverdeau M, Higgs R, Stefanska A, Groom JR, et al. Retinoic acid expression associates with enhanced IL-22 production by gammadelta T cells and innate lymphoid cells and attenuation of intestinal inflammation. J Exp Med. 2013;210(6):1117–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Mora JR, Iwata M, Eksteen B, Song SY, Junt T, Senman B, et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science. 2006;314(5802):1157–60.

    Article  CAS  PubMed  Google Scholar 

  86. Feng T, Cong Y, Qin H, Benveniste EN, Elson CO. Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid. J Immunol. 2010;185(10):5915–25.

    Article  CAS  PubMed  Google Scholar 

  87. Maruya M, Suzuki K, Fujimoto H, Miyajima M, Kanagawa O, Wakayama T, et al. Vitamin A-dependent transcriptional activation of the nuclear factor of activated T cells c1 (NFATc1) is critical for the development and survival of B1 cells. Proc Natl Acad Sci U S A. 2011;108(2):722–7.

    Article  CAS  PubMed  Google Scholar 

  88. Di Caro V, Phillips B, Engman C, Harnaha J, Trucco M, Giannoukakis N. Retinoic acid-producing, ex-vivo-generated human tolerogenic dendritic cells induce the proliferation of immunosuppressive B lymphocytes. Clin Exp Immunol. 2013;174(2):302–17.

    PubMed  PubMed Central  Google Scholar 

  89. Cassani B, Villablanca EJ, De Calisto J, Wang S, Mora JR. Vitamin A and immune regulation: role of retinoic acid in gut-associated dendritic cell education, immune protection and tolerance. Mol Asp Med. 2012;33(1):63–76.

    Article  CAS  Google Scholar 

  90. Hong K, Zhang Y, Guo Y, Xie J, Wang J, He X, et al. All-trans retinoic acid attenuates experimental colitis through inhibition of NF-kappaB signaling. Immunol Lett. 2014;162(1 Pt A):34–40.

    Article  CAS  PubMed  Google Scholar 

  91. Chenery A, Burrows K, Antignano F, Underhill TM, Petkovich M, Zaph C. The retinoic acid-metabolizing enzyme Cyp26b1 regulates CD4 T cell differentiation and function. PLoS One. 2013;8(8):e72308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Abdolahi M, Yavari P, Honarvar NM, Bitarafan S, Mahmoudi M, Saboor-Yaraghi AA. Molecular mechanisms of the action of vitamin A in Th17/Treg axis in multiple sclerosis. J Mol Neurosci. 2015;57(4):605–13.

    Article  CAS  PubMed  Google Scholar 

  93. Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med. 2009;361(5):496–509.

    Article  CAS  PubMed  Google Scholar 

  94. Guilliams M, Crozat K, Henri S, Tamoutounour S, Grenot P, Devilard E, et al. Skin-draining lymph nodes contain dermis-derived CD103(-) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells. Blood. 2010;115(10):1958–68.

    Article  CAS  PubMed  Google Scholar 

  95. Giltaire S, Herphelin F, Frankart A, Herin M, Stoppie P, Poumay Y. The CYP26 inhibitor R115866 potentiates the effects of all-trans retinoic acid on cultured human epidermal keratinocytes. Br J Dermatol. 2009;160(3):505–13.

    Article  CAS  PubMed  Google Scholar 

  96. Handono K, Firdausi SN, Pratama MZ, Endharti AT, Kalim H. Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus. Clin Rheumatol. 2016;35(3):631–8.

    Article  PubMed  Google Scholar 

  97. Barstad RM, Hamers MJ, Stephens RW, Sakariassen KS. Retinoic acid reduces induction of monocyte tissue factor and tissue factor/factor VIIa-dependent arterial thrombus formation. Blood. 1995;86(1):212–8.

    CAS  PubMed  Google Scholar 

  98. Krivospitskaya O, Elmabsout AA, Sundman E, Soderstrom LA, Ovchinnikova O, Gidlof AC, et al. A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis. Mol Med. 2012;18:712–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Felicio KM, de Souza A, Neto JFA, de Melo FTC, Carvalho CT, Arbage TP, et al. Glycemic variability and insulin needs in patients with type 1 diabetes mellitus supplemented with vitamin D: a pilot study using continuous glucose monitoring system. Curr Diabetes Rev. 2018;14(4):395–403.

    Article  CAS  PubMed  Google Scholar 

  100. Schambach F, Schupp M, Lazar MA, Reiner SL. Activation of retinoic acid receptor-alpha favours regulatory T cell induction at the expense of IL-17-secreting T helper cell differentiation. Eur J Immunol. 2007;37(9):2396–9.

    Article  CAS  PubMed  Google Scholar 

  101. Dzhagalov I, Chambon P, He YW. Regulation of CD8+ T lymphocyte effector function and macrophage inflammatory cytokine production by retinoic acid receptor gamma. J Immunol. 2007;178(4):2113–21.

    Article  CAS  PubMed  Google Scholar 

  102. Yamada H, Mizuno S, Ross AC, Sugawara I. Retinoic acid therapy attenuates the severity of tuberculosis while altering lymphocyte and macrophage numbers and cytokine expression in rats infected with Mycobacterium tuberculosis. J Nutr. 2007;137(12):2696–700.

    Article  CAS  PubMed  Google Scholar 

  103. Suzuki Y, Orellana MA, Schreiber RD, Remington JS. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science. 1988;240(4851):516–8.

    Article  CAS  PubMed  Google Scholar 

  104. Hall JA, Bouladoux N, Sun CM, Wohlfert EA, Blank RB, Zhu Q, et al. Commensal DNA limits regulatory T cell conversion and is a natural adjuvant of intestinal immune responses. Immunity. 2008;29(4):637–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Immuno-Biology Lab, Translational Health Science and Technology Institute, Faridabad, India

    Suyasha Roy & Amit Awasthi

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  1. Suyasha Roy
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  2. Amit Awasthi
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Correspondence to Amit Awasthi .

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Editors and Affiliations

  1. Department Cellular and Molecular Nutrition, Tehran University of Medical Sciences and Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Maryam Mahmoudi

  2. Research Center for Immunodeficiencies, Tehran University of Medical Sciences and Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Nima Rezaei

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Roy, S., Awasthi, A. (2019). Vitamin A and the Immune System. In: Mahmoudi, M., Rezaei, N. (eds) Nutrition and Immunity. Springer, Cham. https://doi.org/10.1007/978-3-030-16073-9_3

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  • DOI: https://doi.org/10.1007/978-3-030-16073-9_3

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