Vitamin D and immune function: Autocrine, paracrine or endocrine?

Scandinavian Journal of Clinical and Laboratory Investigation

Volumn 72, Issue SUPPL. 243, 2012, Pages 92-102

  Hewison, Martin ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Adaptive immunity; Antibacterial; Innate immunity; Intracrine; Paracrine

Indexed keywords

CALCITRIOL; TOLL LIKE RECEPTOR; VITAMIN D;

ADAPTIVE IMMUNITY; ANTIBACTERIAL ACTIVITY; ANTIGEN PRESENTATION; ARTICLE; AUTOCRINE EFFECT; AUTOIMMUNE DISEASE; DENDRITIC CELL; ENDOCRINE GLAND; HUMAN; IMMUNE DYSREGULATION; IMMUNE FUNCTION TEST; IMMUNOCOMPETENT CELL; INFLAMMATORY DISEASE; INNATE IMMUNITY; INTESTINE FLORA; LYMPHOCYTE; LYMPHOCYTE FUNCTION; MACROPHAGE; MONOCYTE; NEUTROPHIL; PARACRINE SIGNALING; PRIORITY JOURNAL; T LYMPHOCYTE; TUBERCULOSIS; VITAMIN D METABOLISM; ANIMAL; IMMUNE SYSTEM; IMMUNOLOGY; INFLAMMATION; PHYSIOLOGY; REVIEW;

ADAPTIVE IMMUNITY; ANIMALS; ANTIGEN PRESENTATION; HUMANS; IMMUNE SYSTEM; IMMUNITY, INNATE; INFLAMMATION; NEUTROPHILS; T-LYMPHOCYTES; TOLL-LIKE RECEPTORS; VITAMIN D;

EID: 84860370099     PISSN: 00365513     EISSN: 15027686     Source Type: Journal    
DOI: 10.3109/00365513.2012.682862     Document Type: Article

References (112)

1. Moller KI, Kongshoj B, Philipsen PA, Thomsen VO, Wulf HC. How Finsen's light cured lupus vulgaris. Photodermatol Photoimmunol Photomed 2005;21:118-124.
2. Grad R. Cod and the consumptive: a brief history of codliver oil in the treatment of pulmonary tuberculosis. Pharmacy in history 2004;46:106-120.
3. Herrera G. Vitamin D in massive doses as an adjuvant to the sulfones in the treatment of tuberculoid leprosy. Int J Lepr 1949;17:35-42.
4. Wilkinson RJ, Llewelyn M, Toossi Z, Patel P, Pasvol G, Lalvani A, et al. Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study. Lancet 2000;355:618-621.
5. Ustianowski A, Shaffer R, Collin S, Wilkinson RJ, Davidson RN. Prevalence and associations of vitamin D deficiency in foreign-born persons with tuberculosis in London. J Infect 2005;50:432-437.
6. Williams B, Williams AJ, Anderson ST. Vitamin D defi-ciency and insufficiency in children with tuberculosis. Pediatr Infect Dis J 2008;27:941-942.
7. Wejse C, Gomes VF, Rabna P, Gustafson P, Aaby P, Lisse IM, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebocontrolled trial. Am J Respir Crit Care Med 2009;179: 843-850.
8. Martineau AR, Wilkinson RJ, Wilkinson KA, Newton SM, Kampmann B, Hall BM, et al. A single dose of vitamin d enhances immunity to mycobacteria. Am J Respir Crit Care Med 2007;176:208-213.
9. Nursyam EW, Amin Z, Rumende CM. The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion. Acta Med Indones 2006;38:3-5.
10. Martineau AR, Timms PM, Bothamley GH, Hanifa Y, Islam K, Claxton AP, et al. High-dose vitamin D(3) during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomised controlled trial. Lancet 2011;377:242-250.
11. Jeng L, Yamshchikov AV, Judd SE, Blumberg HM, Martin GS, Ziegler TR, et al. 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.
12. Gombart AF, Bhan I, Borregaard N, Tamez H, Camargo CA, Jr., Koeffler HP, et al. Low plasma level of cathelicidin antimicrobial peptide (hCAP18) predicts increased infectious disease mortality in patients undergoing hemodialysis. Clin Infect Dis 2009;48:418-424.
13. Cannell JJ, Vieth R, Umhau JC, Holick MF, Grant WB, Madronich S, et al. Epidemic influenza and vitamin D. Epidemiol Infect 2006;134:1129-1140.
14. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 2008;87:1080S-1086S.
15. Adorini L, Penna G. Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol 2008;4:404-412.
16. M athieu C, Gysemans C, Giulietti A, Bouillon R. Vitamin D and diabetes. Diabetologia 2005;48:1247-1257.
17. Littorin B, Blom P, Scholin A, Arnqvist HJ, Blohme G, Bolinder J, et al. Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS). Diabetologia 2006;49:2847-2852.
18. Harris SS. Vitamin D in type 1 diabetes prevention. J Nutr 2005;135:323-325.
19. Ramos-Lopez E, Jansen T, Ivaskevicius V, Kahles H, Klepzig C, Oldenburg J, et al. Protection from type 1 diabetes by vitamin D receptor haplotypes. Ann N Y Acad Sci 2006;1079:327-334.
20. Bailey R, Cooper JD, Zeitels L, Smyth DJ, Yang JH, Walker NM, et al. Association of the vitamin D metabolism gene CYP27B1 with type 1 diabetes. Diabetes 2007.
21. Raghuwanshi A, Joshi SS, Christakos S. Vitamin D and multiple sclerosis. J Cell Biochem 2008;105:338-343.
22. Vagianos K, Bector S, McConnell J, Bernstein CN. Nutrition assessment of patients with inflammatory bowel disease. JPEN J Parenter Enteral Nutr 2007;31:311-319.
23. Pappa HM, Gordon CM, Saslowsky TM, Zholudev A, Horr B, Shih MC, et al. Vitamin D status in children and young adults with inflammatory bowel disease. Pediatrics 2006;118:1950-1961.
24. Pappa HM, Grand RJ, Gordon CM. Report on the vitamin D status of adult and pediatric patients with inflamatory bowel disease and its significance for bone health and disease. Inflamm Bowel Dis 2006;12:1162-1174.
25. Packey CD, Sartor RB. Commensal bacteria, traditional and opportunistic pathogens, dysbiosis and bacterial killing in inflammatory bowel diseases. Curr Opin Infect Dis 2009;22:292-301.
26. Rook GA, Steele J, Fraher L, Barker S, Karmali R, O'Riordan J, et al. Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 1986;57:159-163.
27. Adams JS, Gacad MA. Characterization of 1 alphahydroxylation of vitamin D3 sterols by cultured alveolar macrophages from patients with sarcoidosis. J Exp Med 1985;161:755-765.
28. Papapoulos SE, Clemens TL, Fraher LJ, Lewin IG, Sandler LM, O'Riordan JL. 1, 25-dihydroxycholecalciferol in the pathogenesis of the hypercalcaemia of sarcoidosis. Lancet 1979;1:627-630.
29. Hewison M, Burke F, Evans KN, Lammas DA, Sansom DM, Liu P, et al. Extra-renal 25-hydroxyvitamin D3-1alphahydroxylase in human health and disease. J Steroid Biochem Mol Biol 2007;103:316-321.
30. 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.
31. Reichel H, Koeffler HP, Bishop JE, Norman AW. 25-Hydroxyvitamin D3 metabolism by lipopolysaccharidestimulated normal human macrophages. J Clin Endocrinol Metab 1987;64:1-9.
32. Zehnder D, Bland R, Williams MC, McNinch RW, Howie AJ, Stewart PM, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab 2001;86:888-894.
33. Fu GK, Lin D, Zhang MY, Bikle DD, Shackleton CH, Miller WL, et al. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol Endocrinol 1997;11: 1961-1970.
34. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006;311:1770-1773.
35. Zaiou M, Gallo RL. Cathelicidins, essential gene-encoded mammalian antibiotics. J Mol Med 2002;80:549-561.
36. Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. J Leukoc Biol 2004;75:39-48.
37. Wang TT, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol 2004;173:2909-2912.
38. Gombart AF, Borregaard N, Koeffler HP. 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 2005;19:1067-1077.
39. Gombart AF, Saito T, Koeffler HP. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genomics 2009;10:321.
40. Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, et al. Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 2009;182: 4289-4295.
41. Stoffels K, Overbergh L, Giulietti A, Verlinden L, Bouillon R,Mathieu C. Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes. J Bone Miner Res 2006;21:37-47.
42. Krutzik SR, Hewison M, Liu PT, Robles JA, Stenger S, Adams JS, et al. IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. J Immunol 2008;181:7115-7120.
43. Liu PT, Schenk M, Walker VP, Dempsey PW, Kanchanapoomi M, Wheelwright M, et al. Convergence of IL1-beta and VDR activation pathways in human TLR2/1-induced antimicrobial responses. PLoS One 2009;4:e5810.
44. Wang TT, Dabbas B, Laperriere D, Bitton AJ, Soualhine H, Tavera-Mendoza LE, et al. Direct and indirect induction by 1,25-dihydroxyvitamin D3 of the NOD2/CARD15-defensin beta2 innate immune pathway defective in Crohn disease. J Biol Chem 285:2227-2231.
45. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science 2000;290:1717-1721.
46. Levine B, Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 2007;7: 767-777.
47. Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, et al. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe 2009;6:231-243.
48. Shin DM, Yuk JM, Lee HM, Lee SH, Son JW, Harding CV, et al. Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell Microbiol 2011;12:1648-1665.
49. Lisse TS, Liu T, Irmler M, Beckers J, Chen H, Adams JS, et al. Gene targeting by the vitamin D response element binding protein reveals a role for vitamin D in osteoblast mTOR signaling. Faseb J 2011;25:937-947.
50. Fabri M, Realegeno SE, Jo EK, Modlin RL. Role of autophagy in the host response to microbial infection and potential for therapy. Curr Opin Immunol 2011;23:65-70.
51. Lisse TS, Hewison M. Vitamin D: a new player in the world of mTOR signaling. Cell Cycle 2011;10:1888-1889.
52. Edfeldt K, Liu PT, Chun R, Fabri M, Schenk M, Wheelwright M, et al. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc Natl Acad Sci U S A 2010;107:22593-22598.
53. Fabri M, Stenger S, Shin DM, Yuk JM, Liu PT, Realegeno S, et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci Transl Med 2011;3:104ra102.
54. Sakaki T, Kagawa N, Yamamoto K, Inouye K. Metabolism of vitamin D3 by cytochromes P450. Front Biosci 2005;10:119-134.
55. Yim S, Dhawan P, Ragunath C, Christakos S, Diamond G. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25- dihydroxyvitamin D(3). J Cyst Fibros 2007;6:403-410.
56. Evans KN, Nguyen L, Chan J, Innes BA, Bulmer JN, Kilby MD, et al. Effects of 25-hydroxyvitamin D3 and 1, 25-dihydroxyvitamin D3 on cytokine production by human decidual cells. Biol Reprod 2006;75:816-822.
57. Liu N, Kaplan AT, Low J, Nguyen L, Liu GY, Equils O, et al. Vitamin D Induces Innate Antibacterial Responses in Human Trophoblasts via an Intracrine Pathway. Biol Reprod 2009;80:398-406.
58. Schauber J, Dorschner RA, Yamasaki K, Brouha B, Gallo RL. Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli. Immunology 2006;118:509-519.
59. Schauber J, Dorschner RA, Coda AB, Buchau AS, Liu PT, Kiken D, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest 2007;117:803-811.
60. Montoya D, Cruz D, Teles RM, Lee DJ, Ochoa MT, Krutzik SR, et al. Divergence of macrophage phagocytic and antimicrobial programs in leprosy. Cell Host Microbe 2009;6:343-353.
61. Yamamura M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, et al. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 1991;254:277-279.
62. Jullien D, Sieling PA, Uyemura K, Mar ND, Rea TH, Modlin RL. IL-15, an immunomodulator of T cell responses in intracellular infection. J Immunol 1997;158:800-806.
63. Liu PT, Wheelwright M, Teles R, Komisopoulou E, Edfeldt K, Ferguson B, et al. MicroRNA-21 targets the vitamin D-dependent antimicrobial pathway in leprosy. Nat Med 2012;18:267-273.
64. Agostini C, Semenzato G. Cytokines in sarcoidosis. Semin Respir Infect 1998;13:184-196.
65. Kallas M, Green F, Hewison M, White C, Kline G. Rare causes of calcitriol-mediated hypercalcemia: a case report and literature review. J Clin Endocrinol Metab 2010;95: 3111-3117.
66. Brennan A, Katz DR, Nunn JD, Barker S, Hewison M, Fraher LJ, et al. Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol. Immunology 1987;61:457-461.
67. 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;164:2405-2411.
68. Adorini L, Penna G, Giarratana N, Uskokovic M. Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. J Cell Biochem 2003;88:227-233.
69. Penna G, Amuchastegui S, Giarratana N, Daniel KC, Vulcano M, Sozzani S, et al. 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. J Immunol 2007;178: 145-153.
70. Hewison M, Freeman L, Hughes SV, Evans KN, Bland R, Eliopoulos AG, et al. Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol 2003;170:5382-5390.
71. Fritsche J, Mondal K, Ehrnsperger A, Andreesen R, Kreutz M. Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells. Blood 2003;102:3314-3316.
72. Griffin MD, Lutz W, Phan VA, Bachman LA, McKean DJ, 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 USA 2001;98:6800-6805.
73. Panda DK, Miao D, Tremblay ML, Sirois J, Farookhi R, Hendy GN, et al. 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;98:7498-7503.
74. Enioutina EY, Bareyan D, Daynes RA. TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses. J Immunol 2009;182:4296-4305.
75. Bhalla AK, Amento EP, Clemens TL, Holick MF, Krane SM. Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. J Clin Endocrinol Metab 1983;57:1308-1310.
76. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 1983;221:1181-1183.
77. Nunn JD, Katz DR, Barker S, Fraher LJ, Hewison M, Hendy GN, et al. Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3. Immunology 1986;59:479-484.
78. Provvedini DM, Manolagas SC. 1 Alpha,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes. J Clin Endocrinol Metab 1989;68: 774-779.
79. Karmali R, Hewison M, Rayment N, Farrow SM, Brennan A, Katz DR, et al. 1,25(OH)2D3 regulates c-myc mRNA levels in tonsillar T lymphocytes. Immunology 1991;74: 589-593.
80. Lemire JM, Archer DC, Beck L, Spiegelberg HL. Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions. J Nutr 1995;125: 1704S-1708S.
81. Overbergh L, Decallonne B, Waer M, Rutgeerts O, Valckx D, Casteels KM, et al. 1alpha,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper 2 immune shift in NOD mice immunized with GAD65 (p524-543). Diabetes 2000;49:1301-1307.
82. Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, 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;167:4974-4980.
83. Harrington LE, Mangan PR, Weaver CT. Expanding the effector CD4 T-cell repertoire: the Th17 lineage. Curr Opin Immunol 2006;18:349-356.
84. Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 2007;25:821-852.
85. Bettelli E, Korn T, Kuchroo VK. Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 2007;19: 652-657.
86. Korn T, Oukka M, Kuchroo V, Bettelli E. Th17 cells: effector T cells with inflammatory properties. Semin Immunol 2007;19:362-371.
87. Chang SH, Chung Y, Dong C. Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression. J Biol Chem 2010;285: 38751-38755.
88. Colin EM, Asmawidjaja PS, van Hamburg JP, Mus AM, van Driel M, Hazes JM, van Leeuwen JP, Lubberts E. 1, 25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis. Arthritis Rheum 2010;62: 132-142.
89. Palmer MT, Lee YK, Maynard CL, Oliver JR, Bikle DD, Jetten AM, et al. Lineage-specific effects of 1, 25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem 2010;286:997-1004.
90. Daniel C, Sartory NA, Zahn N, Radeke HH, Stein JM. Immune modulatory treatment of trinitrobenzene sulfonic acid colitis with calcitriol is associated with a change of a Thelper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther 2008;324:23-33.
91. Liu N, Nguyen L, Chun RF, Lagishetty V, Ren S, Wu S, et al. Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation. Endocrinology 2008;149:4799-4808.
92. Gorman S, Kuritzky LA, Judge MA, Dixon KM, McGlade JP, Mason RS, et al. Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4-CD25-cells in the draining lymph nodes. J Immunol 2007;179: 6273-6283.
93. Gregori S, Giarratana N, Smiroldo S, Uskokovic M, Adorini L. A 1alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice. Diabetes 2002;51:1367-1374.
94. Mathieu C, Badenhoop K. Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 2005;16:261-266.
95. Spach KM, Nashold FE, Dittel BN, Hayes CE. IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol 2006;177:6030-6037.
96. Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison M, et al. 1,25-Dihydroxyvitamin D(3) and IL-2 combine to inhibit T cell production of inflamatory cytokines and promote development of regulatory T cells expressing CTLA-4 and FoxP3. J Immunol 2009;183: 5458-5467.
97. Urry Z, Xystrakis E, Richards DF, McDonald J, Sattar Z, Cousins DJ, et al. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1alpha,25-dihydroxyvitamin D3 abrogates regulatory function. J Clin Invest 2009;119:387-398.
98. Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol 2001;167:1945-1953.
99. Dong X, Bachman LA, Kumar R, Griffin MD. Generation of antigen-specific, interleukin-10-producing T-cells using dendritic cell stimulation and steroid hormone conditioning. Transpl Immunol 2003;11:323-333.
100. Adorini L, Penna G, Giarratana N, Roncari A, Amuchastegui S, Daniel KC, et al. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. J Steroid Biochem Mol Biol 2004;89-90:437-441.
101. Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys 2000;374:334-338.
102. Iho S, Iwamoto K, Kura F, Okuno Y, Takahashi T, Hoshino T. Mechanism in 1,25(OH)2D3-induced suppression of helper/suppressor function of CD4/CD8 cells to immunoglobulin production in B cells. Cell Immunol 1990;127:12-25.
103. Yu S, Bruce D, Froicu M, Weaver V, Cantorna MT. Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice. Proc Natl Acad Sci USA 2008;105:20834-20839.
104. Sigmundsdottir H, Pan J, Debes GF, Alt C, Habtezion A, Soler D, et al. DCs metabolize sunlight-induced vitamin D3 to'program ' T cell attraction to the epidermal chemokine CCL27. Nat Immunol 2007;8:285-293.
105. Topilski I, Flaishon L, Naveh Y, Harmelin A, Levo Y, Shachar I. The anti-inflammatory effects of 1, 25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. Eur J Immunol 2004;34:1068-1076.
106. Meehan TF, DeLuca HF. 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;99:5557-5560.
107. Cantorna MT, Hayes CE, DeLuca HF. 1, 25-Dihydroxyvitamin D3 reversibly blocks the progression of relapsing encephalomyelitis, a model of multiple sclerosis. Proc Natl Acad Sci U S A 1996;93:7861-7864.
108. Shiozawa K, Shiozawa S, Shimizu S, Fujita T. 1 alpha, 25-dihydroxyvitamin D3 inhibits pokeweed mitogenstimulated human B-cell activation: an analysis using serumfree culture conditions. Immunology 1985;56:161-167.
109. Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC. 1 alpha,25-Dihydroxyvitamin D3-binding macromolecules in human B lymphocytes: effects on immunoglobulin production. J Immunol 1986;136:2734-2740.
110. Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE. Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol 2007;179:1634-1647.
111. Takahashi K, Nakayama Y, Horiuchi H, Ohta T, Komoriya K, Ohmori H, et al. Human neutrophils express messenger RNA of vitamin D receptor and respond to 1alpha, 25-dihydroxyvitamin D3. Immunopharmacol Immunotoxicol 2002;24:335-347.
112. Sorensen O, Cowland JB, Askaa J, Borregaard N. An ELISA for hCAP-18, the cathelicidin present in human neutrophils and plasma. J Immunol Methods 1997;206:53-59.