Journal List > J Korean Rheum Assoc > v.17(1) > 1003716

Kang: Vitamin D and Immune Responses

Abstract

Vitamins and their metabolites are essential for many physiological processes including immune response. In addition to regulating calcium homeostasis, vitamin D exerts various effects on cells of the immune system, such as macrophages, dendritic cells as well as, B and T cells. Low vitamin D levels are found in patients with autoimmune diseases, which suggest a potential role of vitamin D in autoimmunity. In this review, we discuss the roles of vitamin D in modulating immune responses and the clinical potential of vitamin D metabolites for preventing and treating inflammatory and autoimmune diseases.

REFERENCES

1). Mora JR., Iwata M., von Andrian UH. Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol. 2008. 8:685–98.
crossref
2). Holick MF. Vitamin D deficiency. N Engl J Med. 2007. 357:266–81.
crossref
3). Arnson Y., Amital H., Shoenfeld Y. Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis. 2007. 66:1137–42.
crossref
4). Holick MF. McCollum Award Lecture, 1994: vitamin D-new horizons for the 21st century. Am J Clin Nutr. 1994. 60:619–30.
crossref
5). Sigmundsdottir H. DCs metabolize sunlight-induced vitamin D3 to 'program' T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007. 8:285–93.
crossref
6). Fritsche J., Mondal K., Ehrnsperger A., Andreesen R., Kreutz M. Regulation of 25-hydroxyvitamin D3-1aL-hydroxylase and production of 1aL, 25-dihydroxyvitamin D3 by human dendritic cells. Blood. 2003. 102:3314–6.
7). Monkawa T., Yoshida T., Hayashi M., Saruta T. Identification of 25-hydroxyvitamin D3 1aL-hydroxylase gene expression in macrophages. Kidney Int. 2000. 58:559–68.
8). van Etten E., Mathieu C. Immunoregulation by 1, 25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol. 2005. 97:93–101.
9). 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. 170:5382–90.
crossref
10). Provvedini DM., Tsoukas CD., Deftos LJ., Manolagas SC. 1, 25-dihydroxyvitamin D3 receptors in human leukocytes. Science. 1983. 221:1181–3.
11). 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. 57:1308–10.
12). Lemire JM., Adams JS., Sakai R., Jordan SC. 1aL,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest. 1984. 74:657–61.
13). Bhalla AK., Amento EP., Krane SM. Differential effects of 1, 25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: inhibition of interleukin-2 and augmentation of interleukin-1 production. Cell Immunol. 1986. 98:311–22.
14). Reichel H., Koeffler HP., Tobler A., Norman AW. 1aL,25-dihydroxyvitamin D3 inhibits gM-interferon synthesis by normal human peripheral blood lymphocytes. Proc Natl Acad Sci USA. 1987. 84:3385–9.
15). Meehan MA., Kerman RH., Lemire JM. 1, 25-dihydroxyvitamin D3 enhances the generation of nonspecific suppressor cells while inhibiting the induction of cytotoxic cells in a human MLR. Cell Immunol. 1992. 140:400–9.
16). Alroy I., Towers TL., Freedman LP. 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.
crossref
17). Veldman CM., Cantorna MT., DeLuca HF. Expression of 1, 25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys. 2000. 374:334–8.
18). Cippitelli M., Fionda C., Di Bona D., Di Rosa F., Lupo A., Piccoli M, et al. Negative Regulation of CD95 Ligand Gene Expression by Vitamin D3 in T Lymphocytes. J Immunol. 2002. 168:1154–66.
crossref
19). Reiner SL. Development in motion: helper T cells at work. Cell. 2007. 129:33–6.
crossref
20). Wong CK., Lit LC., Tam LS., Li EK., Wong PT., Lam CW. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in autoimmunity. Clin Immunol. 2008. 127:385–93.
crossref
21). Lyssuk EY., Torgashina AV., Soloviev SK., Nassonov EL., Bykovskaia SN. Reduced number and function of CD4+CD25highFoxP3+ regulatory T cells in patients with systemic lupus erythematosus. Adv Exp Med Biol. 2007. 601:113–9.
22). 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 T helper (Th) 1/Th17 to a Th2 and regulatory T cell profile. J Pharmacol Exp Ther. 2008. 324:23–33.
crossref
23). Penna G., Amuchastegui S., Cossetti C., Aquilano F., Mariani R., Sanvito F, et al. Treatment of experimental autoimmune prostatitis in nonobese diabetic mice by the vitamin D receptor agonist elocalcitol. J Immunol. 2006. 177:8504–11.
crossref
24). 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. 179:6273–83.
25). Chen S., Sims GP., Chen XX., Gu YY., Lipsky PE. Modulatory effects of 1, 25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol. 2007. 179:1634–47.
26). Xu H., Soruri A., Gieseler RKH., Peters JH. 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. 1993. 38:535–40.
27). Penna G., Adorini L. 1aL,25-dihydroxyvitamin D3 Inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired allore-active T cell activation. J Immunol. 2000. 164:2405–11.
28). Aguado P., del Campo MT., Garces MV., Gonzalez-Casaus ML., Bernad M., Gijon-Banos J, et al. Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int. 2000. 11:739–44.
crossref
29). Oelzner P., Muller A., Deschner F., Huller M., Abendroth K., Hein G, et al. Relationship between disease activity and serum levels of vitamin D metabolites and PTH in rheumatoid arthritis. Calcif Tissue Int. 1998. 62:193–8.
crossref
30). Alarcon GS., Friedman AW., Straaton KV., Moulds JM., Lisse J., Bastian HM, et al. Systemic lupus erythematosus in three ethnic groups: III A comparison of characteristics early in the natural history of the LUMINA cohort. Lupus. 1999. 8:197–209.
crossref
31). Jahnsen J., Falch JA., Mowinckel P., Aadland E. Vitamin D status, parathyroid hormone and bone mineral density in patients with inflammatory bowel disease. Scand J Gastroenterol. 2002. 37:192–9.
crossref
32). Froicu M., Weaver V., Wynn TA., McDowell MA., Welsh JE., Cantorna MT. A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol. 2003. 17:2386–92.
crossref
33). Chan TY. Vitamin D deficiency and susceptibility to tuberculosis. Calcif Tissue Int. 2000. 66:476–8.
crossref
34). Yang S., Smith C., Prahl JM., Luo X., DeLuca HF. Vitamin D deficiency suppresses cell-mediated immunity in vivo. Arch Biochem Biophys. 1993. 303:98–106.
crossref
35). Valdivielso JM., Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 2006. 371:1–12.
crossref
36). Smolders J., Peelen E., Thewissen M., Menheere P., Cohen Tervaert JW., Hupperts R, et al. The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmun Rev. 2009. 8:621–6.
crossref
37). Ozaki Y., Nomura S., Nagahama M., Yoshimura C., Kagawa H., Fukuhara S. Vitamin-D receptor genotype and renal disorder in Japanese patients with systemic lupus erythematosus. Nephron. 2000. 85:86–91.
crossref
38). Huang CM., Wu MC., Wu JY., Tsai FJ. Association of vitamin D receptor gene BsmI polymorphisms in Chinese patients with systemic lupus erythematosus. Lupus. 2002. 11:31–4.
39). Maalej A., Petit-Teixeira E., Michou L., Rebai A., Cornelis F., Ayadi H. Association study of VDR gene with rheumatoid arthritis in the French population. Genes Immun. 2005. 6:707–11.
crossref
40). Abe J. Prevention of immunological disorders in MRL/l mice by a new synthetic analogue of vitamin D3, 22-oxa-1aL,25-dihydroxyvitamin D3. J Nutr Sci Vitaminol (Tokyo). 1990. 36:21–31.
41). Cantorna MT., Hayes CE., DeLuca HF. 1, 25-dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr. 1998. 128:68–72.
42). Larsson P., Mattsson L., Klareskog L., Johnsson C. A vitamin D analogue (MC 1288) has immunomodulatory properties and suppresses collagen-induced arthritis (CIA) without causing hypercalcaemia. Clin Exp Immunol. 1998. 114:277–83.
43). 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. 177:6030–7.
44). Adorini L. Intervention in autoimmunity: the potential of vitamin D receptor agonists. Cell Immunol. 2005. 233:115–24.
crossref
45). Branisteanu DD., Mathieu C., Bouillon R. Synergism between sirolimus and 1, 25-dihydroxyvitamin D3 in vitro and in vivo. J Neuroimmunol. 1997. 79:138–47.
46). Van Etten E., Branisteanu DD., Overbergh L., Bouillon R., Verstuyf A., Mathieu C. Combination of a 1, 25-dihydroxyvitamin D3 analog and a bisphosphonate prevents experimental autoimmune encephalomyelitis and preserves bone. Bone. 2003. 32:397–404.

Fig. 1.
Reciprocal regulation of FOXP3+ T cells and Th17 cells by vitamin D. 1,25(OH)2D3 promotes the development of FOXP3+ CD4 T lymphocytes with regulatory function which also suppresses IL-17 producing CD4 helper T (Th17) cells differentiation.
jkra-17-16f1.tif
TOOLS
Similar articles