Vitamin-D in the immune system: Genomic and non-genomic actions

Mini-Reviews in Medicinal Chemistry

Volumn 15, Issue 11, 2015, Pages 953-963

  Trochoutsou, Aikaterini I ^a   Kloukina, Vaia ^a   Samitas, Konstantinos ^a,b   Xanthou, Georgina ^a  

^a BIOMEDICAL RESEARCH FOUNDATION   (Greece)

^b Athens Chest Hospital   (Greece)

Author keywords

Calcitriol; Inflammation; Innate and adaptive immune responses; Vitamin D; Vitamin D receptor

Indexed keywords

VITAMIN D; VITAMIN D RECEPTOR; CALCITRIOL RECEPTOR; CYTOCHROME P450; CYTOKINE;

ARTICLE; B LYMPHOCYTE; CHEMICAL STRUCTURE; DENDRITIC CELL; HUMAN; HYDROXYLATION; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOREGULATION; INFLAMMATION; INNATE IMMUNITY; NONHUMAN; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; VITAMIN D DEFICIENCY; VITAMIN SUPPLEMENTATION; ADAPTIVE IMMUNITY; ANALOGS AND DERIVATIVES; DRUG EFFECTS; GENETICS; IMMUNOLOGY; MACROPHAGE; METABOLISM;

ADAPTIVE IMMUNITY; B-LYMPHOCYTES; CYTOCHROME P-450 ENZYME SYSTEM; CYTOKINES; DENDRITIC CELLS; HUMANS; IMMUNITY, INNATE; MACROPHAGES; RECEPTORS, CALCITRIOL; SIGNAL TRANSDUCTION; VITAMIN D;

EID: 84937128790     PISSN: 13895575     EISSN: 18755607     Source Type: Journal    
DOI: 10.2174/1389557515666150519110830     Document Type: Article

References (121)

1. Colston, K.; Colston, M.J.; Feldman D. 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture. Endocrinology, 1981, 108, 1083-6.
2. Manolagas, S.C.; Haussler, M.R.; Deftos, L.J. 1,25-dihydroxyvitamin D3 receptors in cancer. Lancet, 1980, 1, 828.
3. White, J.H. Vitamin D signaling, infectious diseases, and regulation of innate immunity. Infect. Immun., 2008, 76, 3837-43.
4. Hewison M. Vitamin D and innate and adaptive immunity. Vit. Horm., 2011, 86, 23-62.
5. Wobke, T.K.; Sorg, B.L.; Steinhilber D. Vitamin D in inflammatory diseases. Front Physiol., 2014, 5, 244.
6. Delvin, E.; Souberbielle, J.C.; Viard, J.P.; Salle, B. Role of vitamin D in acquired immune and autoimmune diseases. Crit. Rev. Clin. Lab. Sci., 2014, 51, 232-47.
7. Korf, H.; Decallonne, B.; Mathieu, C. Vitamin D for infections. Curr. Opin. Endocrinol. Diabetes. Obes., 2014, 21, 431-6.
8. Hewison, M. Antibacterial effects of vitamin D. Nat. Rev. Endocrinol., 2011, 7, 337-45.
9. Haussler, M.R.; Jurutka, P.W.; Mizwicki, M.; Norman, A.W. Vitamin D receptor (VDR)-mediated actions of 1alpha,25(OH)(2)vitamin D(3), genomic and non-genomic mechanisms. Best Pract. Res. Clin. Endocrinol. Metab., 2011, 25, 543-59.
10. Mizwicki, M.T.; Keidel, D.; Bula, C.M.; Bishop, J.E.; Zanello, L.P.; Wurtz, J.M.; Moras, D.; Norman, A.W. Identification of an alternative ligand-binding pocket in the nuclear vitamin D receptor and its functional importance in 1alpha,25(OH)2-vitamin D3 signaling. Proc. Natl. Acad. Sci. U.S.A., 2004, 101, 12876-81.
11. Mizwicki, M.T.; Menegaz, D.; Yaghmaei, S.; Henry, H.L.; Norman, A.W. A molecular description of ligand binding to the two overlapping binding pockets of the nuclear vitamin D receptor (VDR): structure-function implications. J. Steroid Biochem. Mol. Biol., 2010, 121, 98-105.
12. Sterling, K.A.; Eftekhari, P., Girndt, M.; Kimmel, P.L.; Raj, D.S. The immunoregulatory function of vitamin D: implications in chronic kidney disease. Nat. Rev. Nephrol., 2012, 8, 403-12.
13. Blunt, J.W.; Tanaka, Y.; DeLuca, H.F. Biological activity of 25-hydroxycholecalciferol, a metabolite of vitamin D3. Proc. Natl. Acad. Sci. U.S.A., 1968, 61, 1503-6.
14. Henry, H.L. Regulation of vitamin D metabolism. Best Pract. Res. Clin. Endocrinol. Metab., 2011, 25, 531-41.
15. Jones, G. Expanding role for vitamin D in chronic kidney disease: importance of blood 25-OH-D levels and extra-renal 1alphahydroxylase in the classical and nonclassical actions of 1alpha,25-dihydroxyvitamin D(3). Semin. Dial, 2007, 20, 316-24.
16. Wang, Y.; Zhu, J.; DeLuca, H.F. Where is the vitamin D receptor? Arch. Biochem. Biophys., 2012, 523, 123-33.
17. Haussler, M.R.; Norman, A.W. Chromosomal receptor for a vitamin D metabolite. Proc. Natl. Acad. Sci. U.S.A., 1969, 62, 155-62.
18. Margolis, R.N.; Christakos, S. The nuclear receptor superfamily of steroid hormones and vitamin D gene regulation. An update. Ann. NY Acad. Sci., 2010, 1192, 208-14.
19. Rochel, N.; Tocchini-Valentini, G.; Egea, P.F.; Juntunen, K.; Garnier, J.M.; Vihko, P.; Moras, D. Functional and structural characterization of the insertion region in the ligand binding domain of the vitamin D nuclear receptor. Eur. J. Biochem., 2001, 268, 971-9.
20. Rochel, N.; Wurtz, J.M.; Mitschler, A.; Klaholz, B.; Moras, D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell, 2000, 5, 173-9.
21. Haussler, M.R.; Haussler, C.A.; Jurutka, P.W.; Thompson, P.D.; Hsieh, J.C.; Remus, L.S.; Selznick, S.H.; Whitfield, G.K. The vitamin D hormone and its nuclear receptor: molecular actions and disease states. J. Endocrinol., 1997, 154 Suppl, S57-S73.
22. Dilworth FJ, Chambon P. Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription. Oncogene, 2001, 20, 3047-54.
23. McKenna NJ, O'Malley BW. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell, 2002, 108, 465-74.
24. Hammes SR, Levin ER. Extranuclear steroid receptors: nature and actions. Endocr. Rev., 2007, 28, 726-41.
25. Losel R, Wehling M. Nongenomic actions of steroid hormones. Nat Rev. Mol. Cell Biol., 2003, 4, 46-56.
26. Larriba MJ, Gonzalez-Sancho JM, Bonilla F, Munoz A. Interaction of vitamin D with membrane-based signaling pathways. Front Physiol., 2014, 5, 60.
27. Nemere I, Dormanen MC, Hammond MW, Okamura WH, Norman AW. Identification of a specific binding protein for 1 alpha,25-dihydroxyvitamin D3 in basal-lateral membranes of chick intestinal epithelium and relationship to transcaltachia. J. Biol. Chem., 1994, 269, 23750-6.
28. Bouillon R, Okamura WH, Norman AW. Structure-function relationships in the vitamin D endocrine system. Endocr. Rev., 1995, 16, 200-57.
29. Huhtakangas JA, Olivera CJ, Bishop JE, Zanello LP, Norman AW. The vitamin D receptor is present in caveolae-enriched plasma membranes and binds 1 alpha,25(OH)2-vitamin D3 in vivo and in vitro. Mol. Endocrinol., 2004, 18, 2660-71.
30. Norman AW, Olivera CJ, Barreto Silva FR, Bishop JE. A specific binding protein/receptor for 1alpha,25-dihydroxyvitamin D(3) is present in an intestinal caveolae membrane fraction. Biochem. Biophys. Res. Commun., 2002, 298, 414-9.
31. Mizwicki MT, Norman AW. The vitamin D sterol-vitamin D receptor ensemble model offers unique insights into both genomic and rapid-response signaling. Sci. Signal., 2009, 2, re4.
32. Abe E, Miyaura C, Sakagami H, Takeda M, Konno K, Yamazaki T, Yoshiki S, Suda T. Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3. Proc. Natl. Acad. Sci. U.S.A., 1981, 78, 4990-4.
33. Abe E, Miyaura C, Tanaka H, Shiina Y, Kuribayashi T, Suda S, Nishii Y, DeLuca HF, Suda T. 1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism. Proc. Natl. Acad. Sci. U.S.A., 1983, 80, 5583-7.
34. Koeffler HP, Amatruda T, Ikekawa N, Kobayashi Y, DeLuca HF. Induction of macrophage differentiation of human normal and leukemic myeloid stem cells by 1,25-dihydroxyvitamin D3 and its fluorinated analogues. Cancer Res., 1984, 44, 5624-8.
35. Kreutz M, Andreesen R, Krause SW, Szabo A, Ritz E, Reichel H. 1,25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages. Blood, 1993, 82, 1300-7.
36. Koeffler HP, Reichel H, Bishop JE, Norman AW. gamma-Interferon stimulates production of 1,25-dihydroxyvitamin D3 by normal human macrophages. Biochem. Biophys. Res. Commun., 1985, 127, 596-603.
37. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, Ochoa MT, Schauber J, Wu K, Meinken C, Kamen DL, Wagner M, Bals R, Steinmeyer A, Zugel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 2006, 311, 1770-3.
38. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J. Immunol., 2009, 182, 4289-95.
39. Kim TH, Lee B, Kwon E, Choi SJ, Lee YH, Song GG, Sohn J, Ji JD. Regulation of TREM-1 expression by 1,25-dihydroxyvitamin D3 in human monocytes/macrophages. Immunol. Lett., 2013, 154, 80-5.
40. Lee B, Kwon E, Kim Y, Kim JH, Son SW, Lee JK, Kim DW, Sohn J, Kim TH, Ji JD. 1alpha,25-Dihydroxyvitamin D3 upregulates HIF-1 and TREM-1 via mTOR signaling. Immunol. Lett., 2015, 163, 14-21.
41. Durr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim. Biophys. Acta., 2006, 1758, 1408-25.
42. Gordon, Y.J.; Huang, L.C.; Romanowski, E.G.; Yatesm K.A.; Proske, R.J.; McDermott, A.M. Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity. Curr. Eye Res., 2005, 30, 385-94.
43. Nijnik, A.; Hancock, R.E. The roles of cathelicidin LL-37 in immune defences and novel clinical applications. Curr. Opin. Hematol., 2009, 16, 41-7.
44. Nizet, V.; Ohtake, T.; Lauth, X.; Trowbridge, J.; Rudisill, J.; Dorschner, R.A.; Pestonjamasp, V.; Piraino, J.; Huttner, K.; Gallo, R.L. Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature, 2001, 414, 454-7.
45. Krutzik, S.R.; Hewison, M.; Liu, P.T.; Robles, J.A.; Stenger, S.; Adams, J.S.; Modlin, R.L. IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. J. Immunol., 2008, 181, 7115-20.
46. Chen, Y.; Liu, W.; Sun, T.; Huang, Y.; Wang, Y.; Deb, D.K.; Yoon, D.; Kong, J.; Thadhani, R.; Li, Y.C. 1,25-Dihydroxyvitamin D promotes negative feedback regulation of TLR signaling via targeting microRNA-155-SOCS1 in macrophages. J. Immunol., 2013, 190, 3687-95.
47. Andress, D.L. Vitamin D in chronic kidney disease, a systemic role for selective vitamin D receptor activation. Kidney Int., 2006, 69, 33-43.
48. Bikle, D.D. Vitamin D and the immune system, role in protection against bacterial infection. Curr. Opin. Nephrol. Hypertens., 2008, 17,348-52.
49. Hewison, M. Vitamin D and the immune system, new perspectives on an old theme. Endocrinol. Metab. Clin. North Am., 2010, 39, 365-79, table.
50. Maalouf, N.M. The noncalciotropic actions of vitamin D, recent clinical developments. Curr. Opin. Nephrol. Hypertens., 2008, 17, 408-15.
51. Kankova, M.; Luini, W.; Pedrazzoni, M.; Riganti, F.; Sironi, M.; Bottazzi, B.; Mantovani, A.; Vecchi, A. Impairment of cytokine production in mice fed a vitamin D3-deficient diet. Immunology, 1991, 73, 466-71.
52. Di, R.M.; Malaguarnera, G.; De, G.C.; Palumbo, M.; Nunnari, G.; Malaguarnera, L. Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages. Cell Immunol., 2012, 280, 36-43.
53. Zhang, Y.; Leung, D.Y.; Richers, B.N.; Liu, Y.; Remigio, L.K.; Riches, D.W.; Goleva, E. Vitamin D inhibits monocyte/ macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J. Immunol., 2012, 188, 2127-35.
54. Sadeghi, K.; Wessner, B.; Laggner, U.; Ploder, M.; Tamandl, D.; Friedl, J.; Zugel, U.; Steinmeyer, A.; Pollak, A.; Roth, E.; Boltz-Nitulescu, G.; Spittler, A. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogenassociated molecular patterns. Eur. J. Immunol., 2006, 36, 361-70.
55. Svajger, U.; Obermajer, N.; Jeras, M. Novel findings in druginduced dendritic cell tolerogenicity. Int. Rev. Immunol., 2010, 29, 574-607.
56. Maldonado, R.A.; von Andrian, U.H. How tolerogenic dendritic cells induce regulatory T cells. Adv. Immunol., 2010, 108, 111-65.
57. Pulendran, B.; Tang, H.; Manicassamy, S. Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat. Immunol., 2010, 11, 647-55.
58. Everts, B.; Pearce, E.J. Metabolic control of dendritic cell activation and function, recent advances and clinical implications. Front Immunol., 2014, 5, 203.
59. Brennan, A.; Katz, D.R.; Nunn, J.D.; Barker, S.; Hewison, M.; Fraher, L.J.; O'Riordan, J.L. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology, 1987, 61, 457-61.
60. Dam, T.N.; Moller, B.; Hindkjaer, J.; Kragballe, K. The vitamin D3 analog calcipotriol suppresses the number and antigen-presenting function of Langerhans cells in normal human skin. J. Inv. Dermatol. Symp. Proc., 1996, 1, 72-7.
61. Penna, G.; Adorini, L. 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J. Immunol., 2000, 164, 2405-11.
62. Takeda, M.; Yamashita, T.; Sasaki, N.; Nakajima, K.; Kita, T.; Shinohara, M.; Ishida, T.; Hirata, K. Oral administration of an active form of vitamin D3 (calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic functions. Arterioscler Thromb. Vasc. Biol., 2010, 30, 2495-503.
63. Zhang, Y.; Leung, D.Y.; Richers, B.N.; Lium Y.; Remigio, L.K.; Riches, D.W.; Goleva, E. Vitamin D inhibits monocyte/ macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J. Immunol., 2012, 188, 2127-35.
64. Hewison, M.; Freeman, L.; Hughes, S.V.; Evans, K.N.; Bland, R.; Eliopoulos, A.G.; Kilby, M.D.; Moss, P.A.; Chakraverty, R. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J. Immunol., 2003, 170, 5382-90.
65. Hewison M, Zehnder D, Chakraverty R, Adams JS. Vitamin D and barrier function, a novel role for extra-renal 1 alpha-hydroxylase. Mol. Cell Endocrinol., 2004, 215, 31-8.
66. Enioutina, E.Y.; Bareyan, D.; Daynes, R.A. TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses. J. Immunol., 2009, 182, 4296-305.
67. Griffin, M.D.; Lutz, W.; Phan, V.A.; Bachman, L.A.; McKean, D.J.; Kumar, R. Dendritic cell modulation by 1alpha,25 dihydroxyvitamin D3 and its analogs, a vitamin D receptordependent pathway that promotes a persistent state of immaturity in vitro and in vivo. Proc. Natl. Acad. Sci. U.S.A., 2001, 98, 6800-5.
68. Panda, D.K.; Miao, D.; Tremblay, M.L.; Sirois, J.; Farookhi, R.; Hendy, G.N.; Goltzman, D. Targeted ablation of the 25-hydroxyvitamin D 1alpha-hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc. Natl. Acad. Sci. U.S.A., 2001, 98, 7498-503.
69. Griffin, M.D.; Lutz, W.H.; Phan, V.A.; Bachman, L.A.; McKean, D.J.; Kumar, R. Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs. Biochem. Biophys. Res. Commun., 2000, 270, 701-8.
70. Liu, Y.J. IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu. Rev. Immunol., 2005, 23, 275-306.
71. Steinman, R.M.; Hawiger, D.; Nussenzweig, M.C. Tolerogenic dendritic cells. Annu. Rev. Immunol., 2003, 21, 685-711.
72. Romagnani, S. Lymphokine production by human T cells in disease states. Annu. Rev. Immunol., 1994, 12, 227-57.
73. Parronchi, P.; De, C.M.; Manetti, R.; Simonelli, C.; Sampognaro, S.; Piccinni, M.P.; Macchia, D.; Maggi, E.; Del, P.G.; Romagnani, S. IL-4 and IFN (alpha and gamma) exert opposite regulatory effects on the development of cytolytic potential by Th1 or Th2 human T cell clones. J. Immunol., 1992, 149, 2977-83.
74. Pulendran, B.; Artis, D. New paradigms in type 2 immunity. Science, 2012, 337, 431-5.
75. Fouser, L.A.; Wright, J.F.; Dunussi-Joannopoulos, K.; Collins, M. Th17 cytokines and their emerging roles in inflammation and autoimmunity. Immunol. Rev., 2008, 226, 87-102.
76. Oukka, M. Th17 cells in immunity and autoimmunity. Ann. Rheum. Dis., 2008, 67 Suppl 3, iii26-iii29.
77. Jabeen, R.; Kaplan, M.H. The symphony of the ninth: the development and function of Th9 cells. Curr. Opin. Immunol., 2012, 24, 303-7.
78. Aujla, S.J.; Chan, Y.R.; Zheng, M.; Fei, M.; Askew, D.J.; Pociask, D.A.; Reinhart, T.A.; McAllister, F.; Edeal, J.; Gaus, K.; Husain, S.; Kreindler, J.L.; Dubin, P.J.; Pilewski, J.M.; Myerburg, M.M.; Mason, C.A.; Iwakura, Y.; Kolls, J.K. IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat. Med., 2008, 14, 275-81.
79. Zheng, Y.; Valdez, P.A.; Danilenko, D.M.; Hu, Y.; Sa, S.M.; Gong, Q.; Abbas, A.R.; Modrusan, Z.; Ghilardi, N.; de Sauvage, F.J.; Ouyang, W. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat. Med., 2008, 14, 282-9.
80. Hewison, M. An update on vitamin D and human immunity. Clin. Endocrinol. (Oxf), 2012, 76, 315-25.
81. Lemire, J.M.; Adams, J.S.; Kermani-Arab, V.; Bakke, A.C.; Sakai, R.; Jordan, S.C. 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. J. Immunol., 1985, 134, 3032-5.
82. Alroy, I.; Towers, T.L.; Freedman, L.P. 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., 1995, 15, 5789-99.
83. Cippitelli, M.; Santoni, A. Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur. J. Immunol., 1998, 28, 3017-30.
84. Matsui, T.; Nakao, Y.; Koizumi, T.; Nakagawa, T.; Fujita, T. 1,25-Dihydroxyvitamin D3 regulates proliferation of activated Tlymphocyte subsets. Life Sci., 1985, 37, 95-101.
85. Rigby, W.F.; Stacy, T.; Fanger, M.W. Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J. Clin. Invest., 1984, 74, 1451-5.
86. Baeke, F.; Korf, H.; Overbergh, L.; Verstuyf, A.; Thorrez, L.; Van, L.L.; Waer, M.; Schuit, F.; Gysemans, C.; Mathieu, C. The vitamin D analog, TX527, promotes a human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation. J. Immunol., 2011, 186, 132-42.
87. Palmer, M.T.; Lee, Y.K.; Maynard, C.L.; Oliver, J.R.; Bikle, D.D.; Jetten, A.M.; Weaver, C.T. Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J. Biol. Chem., 2011, 286, 997-1004.
88. Boonstra, A.; Barrat, F.J.; Crain, C.; Heath, V.L.; Savelkoul, H.F.; O'Garra, A. 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J. Immunol., 2001, 167, 4974-80.
89. Daniel, C.; Sartory, N.A.; Zahn, N.; Radeke, H.H.; Stein, J.M. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J. Pharmacol. Exp. Ther., 2008, 324, 23-33.
90. Cantorna, M.T. Mechanisms underlying the effect of vitamin D on the immune system. Proc. Nutr. Soc., 2010, 69, 286-9.
91. Joshi, S.; Pantalena, L.C.; Liu, X.K.; Gaffen, S.L.; Liu, H.; Rohowsky-Kochan, C.; Ichiyama, K.; Yoshimura, A.; Steinman, L.; Christakos, S.; Youssef, S. 1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A. Mol. Cell Biol., 2011, 31, 3653-69.
92. Jeffery, L.E.; Burke, F.; Mura, M.; Zheng, Y.; Qureshi, O.S.; Hewison, M.; Walker, L.S.; Lammas, D.A.; Raza, K.; Sansom, D.M. 1,25-Dihydroxyvitamin D3 and IL-2 combine to inhibit T cell production of inflammatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J. Immunol., 2009, 183, 5458-67.
93. Cantorna, M.T.; Hullett, D.A.; Redaelli, C.; Brandt, C.R.; Humpal-Winter, J.; Sollinger, H.W.; Deluca, H.F. 1,25-Dihydroxyvitamin D3 prolongs graft survival without compromising host resistance to infection or bone mineral density. Transplantation, 1998, 66, 828-31.
94. Barrat, F.J.; Cua, D.J.; Boonstra, A.; Richards, D.F.; Crain, C.; Savelkoul, H.F.; de Waal-Malefyt, R.; Coffman, R.L.; Hawrylowicz, C.M.; O'Garra, A. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)-and Th2-inducing cytokines. J. Exp. Med., 2002, 195, 603-16.
95. Gorman, S.; Kuritzky, L.A.; Judge, M.A.; Dixon, K.M.; McGlade, J.P.; Mason, R.S.; Finlay-Jones, J.J.; Hart, P.H. Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+ cells in the draining lymph nodes. J. Immunol., 2007, 179, 6273-83.
96. Provvedini, D.M.; Manolagas, S.C. 1 Alpha,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes. J. Clin. Endocrinol. Metab., 1989, 68, 774-9.
97. Vanham, G.; Ceuppens, J.L.; Bouillon, R. T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol. Cell Immunol., 1989, 124, 320-33.
98. Meehan, T.F.; DeLuca, H.F. CD8(+) T cells are not necessary for 1 alpha,25-dihydroxyvitamin D(3) to suppress experimental autoimmune encephalomyelitis in mice. Proc. Natl. Acad. Sci. U S A, 2002, 99, 5557-60.
99. Chen, J.; Bruce, D.; Cantorna, M.T. Vitamin D receptor expression controls proliferation of naive CD8+ T cells and development of CD8 mediated gastrointestinal inflammation. BMC Immunol., 2014, 15, 6.
100. Chen, S.; Sims, G.P.; Chen, X.X.; Gu, Y.Y.; Chen, S.; Lipsky, P.E. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J. Immunol., 2007, 179, 1634-47.
101. Iho, S.; Takahashi, T.; Kura, F.; Sugiyama, H.; Hoshino, T. The effect of 1,25-dihydroxyvitamin D3 on in vitro immunoglobulin production in human B cells. J. Immunol., 1986, 136, 4427-31.
102. Hartmann, B.; Heine, G.; Babina, M.; Steinmeyer, A.; Zugel, U.; Radbruch, A.; Worm, M. Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response. Allergy, 2011, 66, 540-8.
103. Knippenberg, S.; Smolders, J.; Thewissen, M.; Peelen, E.; Tervaert, J.W.; Hupperts, R.; Damoiseaux, J. Effect of vitamin D(3) supplementation on peripheral B cell differentiation and isotype switching in patients with multiple sclerosis. Mult. Scler., 2011, 17, 1418-23.
104. Terrier. B.; Derian, N.; Schoindre, Y.; Chaara, W.; Geri, G.; Zahr, N.; Mariampillai, K.; Rosenzwajg, M.; Carpentier, W.; Musset, L.; Piette, J.C.; Six, A.; Klatzmann, D.; Saadoun, D.; Patrice, C.; Costedoat-Chalumeau, N. Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation. Arthritis Res. Ther., 2012, 14, R221.
105. Nashold, F.E.; Hoag, K.A.; Goverman, J.; Hayes, C.E. Rag-1-dependent cells are necessary for 1,25-dihydroxyvitamin D(3) prevention of experimental autoimmune encephalomyelitis. J. Neuroimmunol., 2001, 119, 16-29.
106. Spach, K.M.; Nashold, F.E.; Dittel, B.N.; Hayes, C.E. IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J. Immunol., 2006, 177, 6030-7.
107. Martineau, A.R.; Timms, P.M.; Bothamley, G.H.; Hanifa, Y.; Islam, K.; Claxton, A.P.; Packe, G.E.; Moore-Gillon, J.C.; Darmalingam, M.; Davidson, R.N.; Milburn, H.J.; Baker, L.V.; Barker, R.D.; Woodward, N.J.; Venton, T.R.; Barnes, K.E.; Mullett, C.J.; Coussens, A.K.; Rutterford, C.M.; Mein, C.A.; Davies, G.R.; Wilkinson, R.J.; Nikolayevskyy, V.; Drobniewski, F.A.; Eldridge, S.M.; Griffiths, C.J. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet, 2011, 377, 242-50.
108. Jeng, L.; Yamshchikov, A.V.; Judd, S.E.; Blumberg, H.M.; Martin, G.S.; Ziegler, T.R.; Tangpricha, V. Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis. J. Transl. Med., 2009, 7, 28.
109. Dixon, B.M.; Barker, T.; McKinnon, T.; Cuomo, J.; Frei, B.; Borregaard, N.; Gombart, A.F. Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults. BMC Res. Notes, 2012, 5, 575.
110. Cannell, J.J.; Vieth, R.; Umhau, J.C.; Holick, M.F.; Grant, W.B.; Madronich, S.; Garland, C.F.; Giovannucci, E. Epidemic influenza and vitamin D. Epidemiol. Infect., 2006, 134, 1129-40.
111. Gombart, A.F.; Bhan, I.; Borregaard, N.; Tamez, H.; Camargo, C.A.; Jr, Koeffler, H.P.; Thadhani, R. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin. Infect. Dis., 2009, 48, 418-24.
112. Packey, C.D.; Sartor, R.B. Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr. Opin. Infect. Dis., 2009, 22, 292-301.
113. Harris, S.S. Vitamin D in type 1 diabetes prevention. J. Nutr., 2005, 135, 323-5.
114. Ramos-Lopez, E.; Jansen, T.; Ivaskevicius, V.; Kahles, H.; Klepzig, C.; Oldenburg, J.; Badenhoop, K. Protection from type 1 diabetes by vitamin D receptor haplotypes. Ann. NY Acad. Sci., 2006, 1079, 327-34.
115. Bailey, R.; Cooper, J.D.; Zeitels, L.; Smyth, D.J.; Yang, J.H.; Walker, N.M.; Hypponen, E.; Dunger, D.B.; Ramos-Lopez, E.; Badenhoop, K.; Nejentsev, S.; Todd, J.A. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes, 2007, 56, 2616-21.
116. Munger, K.L.; Zhang, S.M.; O'Reilly, E.; Hernan, M.A.; Olek, M.J.; Willett, W.C.; Ascherio, A. Vitamin D intake and incidence of multiple sclerosis. Neurology, 2004, 62, 60-5.
117. Correale, J.; Ysrraelit, M.C.; Gaitan, M.I. Gender differences in 1,25 dihydroxyvitamin D3 immunomodulatory effects in multiple sclerosis patients and healthy subjects. J. Immunol., 2010, 185, 4948-58.
118. Spach, K.M.; Hayes, C.E. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J. Immunol., 2005, 175, 4119-26.
119. Neve, A.; Corrado, A.; Cantatore, F.P. Immunomodulatory effects of vitamin D in peripheral blood monocyte-derived macrophages from patients with rheumatoid arthritis. Clin. Exp. Med., 2014, 14, 275-83.
120. Ooi, J.H.; Chen, J.; Cantorna, M.T. Vitamin D regulation of immune function in the gut: why do T cells have vitamin D receptors? Mol. Aspects Med., 2012, 33, 77-82.
121. Hanwell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Chem. Inform., 2012, 4, 17.