Skip to main content
SpringerLink
Log in
Book cover

Principles of Osteoimmunology pp 63–96Cite as

Effects of Vitamin D in the Immune System

  • Chapter

  • 793 Accesses

Abstract

The term “vitamin” for vitamin D reflects the original finding that plants contain a substance able to restore bone metabolism in patients suffering from rickets. Later on, endogenous production of a related molecule in animal and man was recognized, dependent on sufficient sun exposure of the skin and increasing its activity 105 times after further renal metabolism.

This was the discovery of the “hormone” vitamin D3. In the last century, it was discovered that cells outside the renal system were also capable of generating the most active metabolite of vitamin D3, namely 1α,25(OH)2D3, and that this was independent of the hormonal regulatory pathways responsible for homeostasis in bone metabolism. Today we are aware of a large number of different cells and tissues able to generate and metabolize 1α,25(OH)2D3 and, as a counterpart, many cell types have been identified as targets for this molecule. In many ways the properties of this part of the vitamin D family classify it as a mediator with some characteristics of cytokines – except for its steroid nature – with paracrine, autocrine and, only under specific conditions, endocrine functions. Its integral role in the innate and adaptive host defense system is well established now, and in part there is interference as well as independence between the osteological and the immunological branch of the family.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   159.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Adams JS, Chen H, Chun R, Ren S, Wu S, Gacad M, Nguyen L, Ride J, Liu P, Modlin R, Hewison M (2007a) Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin D synthesis and action: the human innate immune response. J Bone Miner Res 22: V20–24

    Article  CAS  Google Scholar 

  • Adams JS, Liu PT, Chun R, Modlin RL, Hewison M (2007b) Vitamin D in defense of the human immune response. Ann N Y Acad Sci 1117: 94–105

    Article  CAS  Google Scholar 

  • Adams JS, Ren S, Liu PT, Chun RF, Lagishetty V, Gombart AF, Borregaard N, Modlin RL, Hewison M (2009) Vitamin d-directed rheostatic regulation of monocyte antibacterial responses. J Immunol 182: 4289–4295

    Article  PubMed  CAS  Google Scholar 

  • Adams JS, Sharma OP, Gacad MA, Singer FR (1983) Metabolism of 25-hydroxyvitamin D3 by cultured pulmonary alveolar macrophages in sarcoidosis. J Clin Invest 72: 1856–1860

    Article  PubMed  CAS  Google Scholar 

  • Adorini L (2005) Intervention in autoimmunity: The potential of vitamin D receptor agonists. Cellular Immunology 233: 115–124

    Article  PubMed  CAS  Google Scholar 

  • Adorini L, Giarratana N, Penna G (2004) Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. Semin Immunol 16: 127–134

    Article  PubMed  CAS  Google Scholar 

  • Adorini L, Penna G (2008) Control of autoimmune diseases by the vitamin D endocrine system. Nat Clin Pract Rheumatol 4: 404–412

    Article  PubMed  CAS  Google Scholar 

  • Adorini L, Penna G (2009) Induction of tolerogenic dendritic cells by vitamin D receptor agonists. Handb Exp Pharmacol 188: 251–273

    Article  PubMed  CAS  Google Scholar 

  • Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124: 783–801

    Article  PubMed  CAS  Google Scholar 

  • Almerighi C, Sinistro A, Cavazza A, Ciaprini C, Rocchi G, Bergamini A (2009) 1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes. Cytokine 45:190–197

    Article  PubMed  CAS  Google Scholar 

  • Annunziato F, Romagnani S (2009a) Do studies in humans better depict Th17 cells? Blood 114: 2213–2219

    Article  CAS  Google Scholar 

  • Anunziato F, Romagnani S (2009b) Heterogeneity of human effector CD4+ T cells. Arthritis Res Ther 11:257

    Article  CAS  Google Scholar 

  • Anonymous (1999) Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. 15. Diabetologia 42: 51–54

    Article  Google Scholar 

  • Arnson Y, Amital H, Shoenfeld Y (2007) Vitamin D and autoimmunity: new aetiological and therapeutic considerations. Ann Rheum Dis 66: 1137–1142

    Article  PubMed  CAS  Google Scholar 

  • Ascherio A, Munger KL, Simon KC (2010) Vitamin D and multiple sclerosis. Lancet Neurol 9: 599–612

    Article  PubMed  Google Scholar 

  • Azizi-Semrad U, Krenbek D, Hofbauer G, Karanikas G, Maldonado-Gonzalez E, Pietschmann P, Willheim M (2010) Cytokine profiling of human peripheral blood CD4+ T lymphocytes reveals a new Th-subpopulation (Th6) characterized by IL-6. Eur Cytokine Netw 21: 105–115

    PubMed  CAS  Google Scholar 

  • Baeke F, Gysemans C, Korf H, Mathieu C (2010a) Vitamin D insufficiency: implications for the immune system. Pediatr Nephrol 25: 1597–1606

    Article  Google Scholar 

  • Baeke F, Korf H, Overbergh L, van Etten E, Verstuyf A, Gysemans C, Mathieu C (2010b) Human T lymphocytes are direct targets of 1,25-dihydroxyvitamin D3 in the immune system. J Steroid Biochem Mol Biol 121: 221–227

    Article  CAS  Google Scholar 

  • Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010c) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10: 482–496

    Article  CAS  Google Scholar 

  • Balato A, Unutmaz D, Gaspari AA (2009) Natural killer T cells: an unconventional T-cell subset with diverse effector and regulatory functions. J Invest Dermatol 129: 1628–1642

    Article  PubMed  CAS  Google Scholar 

  • Barrat FJ, Cua DJ, Boonstra A, Richards DF, Crain C, Savelkoul HF, de Waal-Malefyt R, Coffman RL, Hawrylowicz CM, O’Garra A. (2002) 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.: Mar 4;195(5):603–16

    Article  PubMed  CAS  Google Scholar 

  • Bikle D (2009) Nonclassic actions of vitamin D. J Clin Endocrinol Metab 94: 26–34

    Article  PubMed  CAS  Google Scholar 

  • Boltz-Nitulescu G, Willheim M, Spittler A, Leutmezer F, Tempfer C, Winkler S (1995) Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 α,25-dihydroxyvitamin D3 and cytokines. J Leukoc Biol 58: 256–262

    PubMed  CAS  Google Scholar 

  • Boonstra A, Barrat FJ, Crain C, Heath VL, Savelkoul HF, O’Garra A (2001) 1α,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167: 4974–4980

    PubMed  CAS  Google Scholar 

  • Bringhurst FR, Demay MB, Krane SM, Kronenberg HM (2008) Bone and mineral metabolism in health and disease. In: Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo, J (eds) Harrison’s Principles of Internal Medicine, McGraw Hill, New York, 17th edition, pp 2365–2377

    Google Scholar 

  • Byun DG, Demeure CE, Yang LP, Shu U, Ishihara H, Vezzio N, Gately MK, Delespesse G (1994) In vitro maturation of neonatal human CD8 T lymphocytes into IL-4- and IL-5-producing cells. J Immunol 153: 4862–4871

    PubMed  CAS  Google Scholar 

  • Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, Kleinman K, Gillman MW (2007) Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 85: 788–795

    PubMed  CAS  Google Scholar 

  • Cantorna MT (2011) Why do T cells express the vitamin D receptor? Ann N Y Acad Sci 1217: 77–82

    Article  PubMed  CAS  Google Scholar 

  • Cantorna MT, Hayes CE, DeLuca HF (1998) 1,25-Dihydroxycholecalciferol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 128: 68–72

    PubMed  CAS  Google Scholar 

  • Cantorna MT, Mahon BD (2004) Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med 229: 1136–1142

    CAS  Google Scholar 

  • Cantorna MT, Munsick C, Bemiss C, Mahon BD (2000) 1,25-Dihydroxycholecalciferol prevents and ameliorates symptoms of experimental murine inflammatory bowel disease. J Nutr 130: 2648–2652

    PubMed  CAS  Google Scholar 

  • Cantorna MT, Yu S, Bruce D (2008) The paradoxical effects of vitamin D on type 1 mediated immunity. Mol Aspects Med 29: 369–375

    Article  PubMed  CAS  Google Scholar 

  • Chang JH, Cha HR, Lee DS, Seo KY, Kweon MN (2010) 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of T(H)17 cells to protect against experimental autoimmune encephalomyelitis. PLoS One 5:e12925

    Article  PubMed  CAS  Google Scholar 

  • Chang JM, Kuo MC, Kuo HT, Hwang SJ, Tsai JC, Chen HC, Lai YH (2004) 1-α,25-Dihydroxyvitamin D3 regulates inducible nitric oxide synthase messenger RNA expression and nitric oxide release in macrophage-like RAW 264.7 cells. J Lab Clin Med 143: 14–22

    Article  PubMed  CAS  Google Scholar 

  • Chang SH, Chung Y, Dong C (2010) Vitamin D suppresses Th17 cytokine production by inducing C/EBP homologous protein (CHOP) expression. J Biol Chem 285: 38751–38755

    Article  PubMed  CAS  Google Scholar 

  • Chen S, Sims GP, Chen XX, Gu YY, Chen S, Lipsky PE (2007) Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. J Immunol Aug 1;179(3):1634–47.

    PubMed  CAS  Google Scholar 

  • Chesney RW (2010) Vitamin D and The Magic Mountain: the anti-infectious role of the vitamin. J Pediatr 156: 698–703

    Article  PubMed  Google Scholar 

  • Cippitelli M, Santoni A (1998) Vitamin D3: a transcriptional modulator of the interferon-γ gene. Eur J Immunol 28: 3017–3030

    Article  PubMed  CAS  Google Scholar 

  • Colin EM, Asmawidjaja PS, van Hamburg JP, Mus AM, van Driel M, Hazes JM, van Leeuwen JP, Lubberts E (2010) 1,25-dihydroxyvitamin D3 modulates Th17 polarization and interleukin-22 expression by memory T cells from patients with early rheumatoid arthritis. Arthritis Rheum 62: 132–142

    Article  PubMed  CAS  Google Scholar 

  • Costantino CM, Baecher-Allan CM, Hafler DA (2008) Human regulatory T cells and autoimmunity. 43. Eur J Immunol 38: 921–924

    Article  PubMed  CAS  Google Scholar 

  • Croft, M., L. Carter, S.L. Swain, and R.W. Dutton (1994) Generation of polarized antigen-specific CD8 effector populations: reciprocal action of interleukin (IL)-4 and IL-12 in promoting type 2 versus type 1 cytokine profiles. J Exp Med 180: 1715–1728

    Article  PubMed  CAS  Google Scholar 

  • Cutolo M, Otsa K, Uprus M, Paolino S, Seriolo B (2007) Vitamin D in rheumatoid arthritis. Autoimmun Rev 7: 59–64

    Article  PubMed  CAS  Google Scholar 

  • dÁmbrosio (2006) Regulatory T cells: how do they find their space in the immunological arena? 48. Semin Cancer Biol 16: 91–97

    Article  CAS  Google Scholar 

  • D’Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, Sinigaglia F, Panina-Bordignon P (1998) Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. J Clin Invest 101: 252–262

    Article  PubMed  Google Scholar 

  • Dardalhon V, Awasthi A, Kwon H, Galileos G, Gao W, Sobel RA, Mitsdoerffer M, Strom TB, Elyaman W, Ho IC, Khoury S, Oukka M, Kuchroo VK (2008) IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells. Nat Immunol 9: 1347–1355

    Article  PubMed  CAS  Google Scholar 

  • Demeure CE, Wu CY, Shu U, Schneider PV, Heusser C, Yssel H, Delespesse G (1994) In vitro maturation of human neonatal CD4 T lymphocytes. II. Cytokines present at priming modulate the development of lymphokine production. J Immunol 152: 4775–4782

    PubMed  CAS  Google Scholar 

  • Dimeloe S, Nanzer A, Ryanna K, Hawrylowicz C (2010) Regulatory T cells, inflammation and the allergic response – the role of glucocorticoids and Vitamin D. J Steroid Biochem Mol Biol 120: 86–95

    Article  PubMed  CAS  Google Scholar 

  • Do JE, Kwon SY, Park S, Lee ES (2008) Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behcet’s disease. Rheumatology 47: 840–848

    Article  PubMed  CAS  Google Scholar 

  • Erkkola M, Kaila M, Nwaru BI, Kronberg-Kippilä C, Ahonen S, Nevalainen J, Veijola R, Pekkanen J, Ilonen J, Simell O, Knip M, Virtanen SM (2009) Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy 39: 875–882

    Article  PubMed  CAS  Google Scholar 

  • Fritsch P (2009) Dermatologie und Venerologie für das Studium. Springer, Berlin

    Book  Google Scholar 

  • Froicu M, Weaver V, Wynn TA, McDowell MA, Welsh JE, Cantorna MT (2003) A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases. Mol Endocrinol 17: 2386–2392

    Article  PubMed  CAS  Google Scholar 

  • Fronczak CM, Barón AE, Chase HP, Ross C, Brady HL, Hoffman M, Eisenbarth GS, Rewers M, Norris JM (2003) In utero dietary exposures and risk of islet autoimmunity in children. Diabetes Care 26: 3237–3242

    Article  PubMed  Google Scholar 

  • Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L (2004) NKT cells: what’s in a name? Nat Rev Immunol 4: 231–237

    Article  PubMed  CAS  Google Scholar 

  • Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L (2001) Regulatory T cells induced by 1α,25-dihydroxyvitamin d(3) and mycophenolate mofetil treatment mediate transplantation tolerance. J Immunol 167: 1945–1953

    PubMed  CAS  Google Scholar 

  • Hakim I, Bar-Shavit Z (2003) Modulation of TNF-α expression in bone marrow macrophages: involvement of vitamin D response element. J Cell Biochem 88: 986–998

    Article  PubMed  CAS  Google Scholar 

  • Hamada H, Garcia-Hernandez Mde L, Reome JB, Misra SK, Strutt TM, McKinstry KK, Cooper AM, Swain SL, Dutton RW (2009) Tc17, a unique subset of CD8 T cells that can protect against lethal influenza challenge. J Immunol 182: 3469–3481

    Article  PubMed  CAS  Google Scholar 

  • Hartmann B, Heine G, Babina M, Steinmeyer A, Zügel U, Radbruch A, Worm M (2011) Targeting the vitamin D receptor inhibits the B cell-dependent allergic immune response. Allergy 66: 540–548

    Article  PubMed  CAS  Google Scholar 

  • Heine G, Anton K, Henz BM, Worm M (2002) 1α,25-dihydroxyvitamin D3 inhibits anti-CD40 plus IL-4-mediated IgE production in vitro. Eur J Immunol 32: 3395–3404

    PubMed  CAS  Google Scholar 

  • Heine G, Niesner U, Chang HD, Steinmeyer A, Zügel U, Zuberbier T, Radbruch A, Worm M (2008) 1,25-dihydroxyvitamin D(3) promotes IL-10 production in human B cells. Eur J Immunol 38: 2210–2218

    Article  PubMed  CAS  Google Scholar 

  • Herold G (2008) Innere Medizin. Köln, editor?

    Google Scholar 

  • Hewison M (2010) Vitamin D and the immune system: new perspectives on an old theme. Endocrinol Metab Clin North Am 39: 365–379

    Article  PubMed  CAS  Google Scholar 

  • Hewison M, Freeman L, Hughes SV, Evans KN, Bland R, Eliopoulos AG, Kilby MD, Moss PA, Chakraverty R (2003) Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells. J Immunol 170: 5382–5390

    PubMed  CAS  Google Scholar 

  • Holick MF (2008) Photobiology and noncalcemic actions of Vitamin D. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of Bone Biology, Academic Press, Amsterdam, 3rd edition, pp 800–802

    Google Scholar 

  • Huber M, Heink S, Grothe H, Guralnik A, Reinhard K, Elflein K, Hünig T, Mittrücker HW, Brüstle A, Kamradt T, Lohoff M (2009) A Th17-like developmental process leads to CD8(+) Tc17 cells with reduced cytotoxic activity. Eur J Immunol 39: 1716–1725

    Article  PubMed  CAS  Google Scholar 

  • Hyppönen E (2005) Vitamin D for the prevention of preeclampsia? A hypothesis. Nutr Rev 63: 225–232

    PubMed  Google Scholar 

  • Hyppönen E (2010) Vitamin D and increasing incidence of type 1 diabetes-evidence for an association? Diabetes Obes Metab 12: 737–743

    Article  PubMed  Google Scholar 

  • Hyppönen E, Berry DJ, Wjst M, Power C (2009) Serum 25-hydroxyvitamin D and IgE – a significant but nonlinear relationship. Allergy 64: 613–620

    Article  PubMed  CAS  Google Scholar 

  • Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM (2001) Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 358: 1500–1503

    Article  PubMed  Google Scholar 

  • Hyppönen E, Sovio U, Wjst M, Patel S, Pekkanen J, Hartikainen AL, Järvelinb MR (2004) Infant vitamin D supplementation and allergic conditions in adulthood: northern Finland birth cohort 1966. Ann N Y Acad Sci 1037: 84–95

    Article  PubMed  CAS  Google Scholar 

  • Iho S, Kura F, Sugiyama H, Takahashi T, Hoshino T (1985) The role of monocytes in the suppression of PHA-induced proliferation and IL 2 production of human mononuclear cells by 1,25-dihydroxyvitamin D3. Immunol Lett 11: 331–336

    Article  PubMed  CAS  Google Scholar 

  • Iho S, Takahashi T, Kura F, Sugiyama H, Hoshino T (1986) The effect of 1,25-dihydroxyvitamin D3 on in vitro immunoglobulin production in human B cells. J Immunol 136: 4427–4431

    PubMed  CAS  Google Scholar 

  • Ikeda U, Wakita D, Ohkuri T, Chamoto K, Kitamura H, Iwakura Y, Nishimura T (2010) 1α,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically inhibit the differentiation and expansion of Th17 cells. Immunol Lett 134: 7–16

    Article  PubMed  CAS  Google Scholar 

  • Jäger A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK (2009) Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 183: 7169–7177

    Article  PubMed  CAS  Google Scholar 

  • Jeffery LE, Burke F, Mura M, Zheng Y, Qureshi OS, Hewison M, Walker LS, Lammas DA, Raza K, Sansom DM (2009) 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 183: 5458–5467

    Article  PubMed  CAS  Google Scholar 

  • Jirapongsananuruk O, Melamed I, Leung DY (2000) Additive immunosuppressive effects of 1,25-dihydroxyvitamin D3 and corticosteroids on TH1, but not TH2, responses. J Allergy Clin Immunol 106: 981–985

    Article  PubMed  CAS  Google Scholar 

  • Jordan SC, Lemire JM, Sakai RS, Toyoda M, Adams JS (1990) Exogenous interleukin-2 does not reverse the immunoinhibitory effects of 1,25-dihydroxyvitamin D3 on human peripheral blood lymphocyte immunoglobulin production. Mol Immunol 27: 95–100

    Article  PubMed  CAS  Google Scholar 

  • Kelso A, Troutt AB, Maraskovsky E, Gough NM, Morris L, Pech MH, Thomson JA (1991) Heterogeneity in lymphokine profiles of CD4+ and CD8+ T cells and clones activated in vivo and in vitro. Immunol Rev 123: 85–114

    Article  PubMed  CAS  Google Scholar 

  • Kemeny DM, Noble A, Holmes BJ, Diaz-Sanchez D (1994) Immune regulation: a new role for the CD8+ T cell. Immunol Today 15: 107–110

    Article  PubMed  CAS  Google Scholar 

  • Klaushofer K (2010) Arznei und Vernunft: Osteoporose Knochenbruch-Krankheit, 3.Auflage

    Google Scholar 

  • Kreutz M, Andreesen R (1990) Induction of human monocyte to macrophage maturation in vitro by 1,25-dihydroxyvitamin D3. Blood 76: 2457–2461

    PubMed  CAS  Google Scholar 

  • Kriegel MA, Manson JE, Costenbader KH (2011) Does vitamin d affect risk of developing autoimmune disease?: a systematic review. Semin Arthritis Rheum 40: 512–531

    Article  PubMed  CAS  Google Scholar 

  • Krutzik SR, Hewison M, Liu PT, Robles JA, Stenger S, Adams JS, Modlin RL (2008) IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway. J Immunol 181: 7115–7120

    PubMed  CAS  Google Scholar 

  • Larsson P, Mattsson L, Klareskog L, Johnsson C (1998) A vitamin D analogue (MC 1288) has immunomodulatory properties and suppresses collagen-induced arthritis (CIA) without causing hypercalcaemia. Clin Exp Immunol 114: 277–283

    Article  PubMed  CAS  Google Scholar 

  • Le Gros G, Erard F (1994) Non-cytotoxic, IL-4, IL-S, IL-1O producing CD8+ T cells: their activation and effector functions. Curr Opin Immunol 6: 453–457

    Article  PubMed  Google Scholar 

  • Lemire JM, Adams JS, Sakai R, Jordan SC (1984) 1 α,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells. J Clin Invest 74: 657–661

    Article  PubMed  CAS  Google Scholar 

  • 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, Zügel U, Gallo RL, Eisenberg D, Hewison M, Hollis BW, Adams JS, Bloom BR, Modlin RL (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311: 1770–1773

    Article  PubMed  CAS  Google Scholar 

  • Mahon BD, Wittke A, Weaver V, Cantorna MT (2003) The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem 89: 922–932

    Article  PubMed  CAS  Google Scholar 

  • Mathieu C, Badenhoop K (2005) Vitamin D and type 1 diabetes mellitus: state of the art. Trends Endocrinol Metab 16: 261–266

    Article  PubMed  CAS  Google Scholar 

  • Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG (2004) Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 50:72–77

    Article  PubMed  CAS  Google Scholar 

  • Miller J, Gallo RL (2010) Vitamin D and innate immunity. Dermatol Ther 23: 13–22

    Article  PubMed  Google Scholar 

  • Mora JR, Iwata M, von Andrian UH (2008) Vitamin effects on the immune system: vitamins A and D take centre stage. Nat Rev Immunol 8: 685–698

    Article  PubMed  CAS  Google Scholar 

  • Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7: 145–173

    Article  PubMed  CAS  Google Scholar 

  • Müller K, Bendtzen K (1992) Inhibition of human T lymphocyte proliferation and cytokine production by 1,25-dihydroxyvitamin D3. Differential effects on CD45RA+ and CD45R0+ cells. Autoimmunity 14: 37–43

    Article  PubMed  Google Scholar 

  • Müller K, Bendtzen K (1996) 1,25-Dihydroxyvitamin D3 as a natural regulator of human immune functions. J Investig Dermatol Symp Proc. Apr;1(1): 68–71

    Google Scholar 

  • Müller K, Heilmann C, Poulsen LK, Barington T, Bendtzen K (1991) The role of monocytes and T cells in 1,25-dihydroxyvitamin D3 mediated inhibition of B cell function in vitro. 1Immunopharmacology 21: 121–128

    Article  Google Scholar 

  • Müller K, Odum N, Bendtzen K (1993) 1,25-dihydroxyvitamin D3 selectively reduces interleukin-2 levels and proliferation of human T cell lines in vitro. Immunol Lett 35: 177–182

    Article  PubMed  Google Scholar 

  • Nielen MM, van Schaardenburg D, Lems WF, van de Stadt RJ, de Koning MH, Reesink HW, Habibuw MR, van der Horst-Bruinsma IE, Twisk JW, Dijkmans BA (2006) Vitamin D deficiency does not increase the risk of rheumatoid arthritis: comment on the article by Merlino et al. 121. Arthritis Rheum 54: 3719–3720

    Article  PubMed  Google Scholar 

  • Noble A, Macary PA, Kemeny DM (1995) IFN-γ and IL-4 regulate the growth and differentiation of CD81 T cells into subpopulations with distinct cytokine profiles. J Immunol 155: 2928–2937

    PubMed  CAS  Google Scholar 

  • Norman AW (2008) 1α,25(OH)2 Vitamin D3. In: Bilezikian JP, Raisz LG, Martin TJ (eds) Principles of Bone Biology, Academic Press, Amsterdam, 3rd edition, pp 749–771

    Chapter  Google Scholar 

  • O’Garra A, Murphy K (1994) Role of cytokines in determining T-lymphocyte function. Curr Opin Immunol 6: 458–466

    Article  PubMed  Google Scholar 

  • Palmer MT, Lee YK, Maynard CL, Oliver JR, Bikle DD, Jetten AM, Weaver CT (2011) Lineage-specific effects of 1,25-dihydroxyvitamin D(3) on the development of effector CD4 T cells. J Biol Chem 286: 997–1004

    Article  PubMed  CAS  Google Scholar 

  • Pedersen LB, Nashold FE, Spach KM, Hayes CE (2007) 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking. J Neurosci Res 85: 2480–2490

    Article  PubMed  CAS  Google Scholar 

  • Penna G, Amuchastegui S, Giarratana N, Daniel KC, Vulcano M, Sozzani S, Adorini L (2007) 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. J Immunol 178: 145–153

    PubMed  CAS  Google Scholar 

  • Penna G, Roncari A, Amuchastegui S, Daniel KC, Berti E, Colonna M, Adorini L (2005) Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3. Blood 106: 3490–3497

    Article  PubMed  CAS  Google Scholar 

  • Peterlik M, Cross HS (2006) Dysfunction of the vitamin D endocrine system as common cause for multiple malignant and other chronic diseases. Anticancer Res 26: 2581–2588

    PubMed  CAS  Google Scholar 

  • Peterlik M, Cross HS (2005) Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest. May;35(5):290–304

    Article  PubMed  CAS  Google Scholar 

  • Pierrot-Deseilligny C, Souberbielle JC (2010) Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain 133: 1869–1888

    Article  PubMed  Google Scholar 

  • Provvedini DM, Manolagas SC (1989) 1α,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes. J Clin Endocrinol Metab 68: 774–779

    Article  PubMed  CAS  Google Scholar 

  • Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1983) 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 221: 1181–1183

    Article  PubMed  CAS  Google Scholar 

  • Provvedini DM, Tsoukas CD, Deftos LJ, Manolagas SC (1986) 1 α,25-Dihydroxyvitamin D3-binding macromolecules in human B lymphocytes: effects on immunoglobulin production. J Immunol 136: 2734–2740

    PubMed  CAS  Google Scholar 

  • Rigby WF, Stacy T, Fanger MW (1984) Inhibition of T lymphocyte mitogenesis by 1,25-dihydroxyvitamin D3 (calcitriol). J Clin Invest 74: 1451–1455

    Article  PubMed  CAS  Google Scholar 

  • Robinson DS (2009) Regulatory T cells and asthma. Clin Exp Allergy 39: 1314–1323

    Article  PubMed  CAS  Google Scholar 

  • Rockett KA, Brookes R, Udalova I, Vidal V, Hill AV, Kwiatkowski D (1998) 1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun 66: 5314–5321

    PubMed  CAS  Google Scholar 

  • Sadeghi K, Wessner B, Laggner U, Ploder M, Tamandl D, Friedl J, Zügel U, Steinmeyer A, Pollak A, Roth E, Boltz-Nitulescu G, Spittler A (2006) Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol 36: 361–370

    Article  PubMed  CAS  Google Scholar 

  • Salgame P, Abrams JS, Clayberger C, Goldstein H, Convit J, Modlin RL, Bloom BR (1991) Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones. Science 254: 279–282

    Article  PubMed  CAS  Google Scholar 

  • Seder RA, Boulay JL, Finkelman F, Barbier S, Ben-Sasson SZ, Le Gros G, Paul WE (1992) CD8+T Cells can be primed in vitro to produce IL-4. J Immunol 148: 1652–1656

    PubMed  CAS  Google Scholar 

  • Seder RA, Paul WE (1994) Acquisition of lymphokine-producing phenotype by CD4+ T cells. Annu Rev Immunol 12: 635–673

    Article  PubMed  CAS  Google Scholar 

  • Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML (2011) Vitamin D levels and food and environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005–2006. J Allergy Clin Immunol 127: 1195–1202

    Article  PubMed  CAS  Google Scholar 

  • Smith KA (1988) Interleukin-2: inception, impact, and implications. Science 240: 1169–1176

    Article  PubMed  CAS  Google Scholar 

  • Smith KA, Popmihajlov Z (2008).The quantal theory of immunity and the interleukin-2-dependent negative feedback regulation of the immune response.Immunol Rev 224: 124–140

    Article  PubMed  CAS  Google Scholar 

  • Smolders J, Damoiseaux J, Menheere P, Hupperts R (2008) Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol 194: 7–17

    Article  PubMed  CAS  Google Scholar 

  • Smolders J, Peelen E, Thewissen M, Cohen Tervaert JW, Menheere P, Hupperts R, Damoiseaux J (2010) Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One 5: e15235

    Article  PubMed  CAS  Google Scholar 

  • Smolders J, Thewissen M, Peelen E, Menheere P, Tervaert JW, Damoiseaux J, Hupperts R (2009) Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS One 4: e6635

    Article  PubMed  CAS  Google Scholar 

  • Spittler A, Willheim M, Leutmezer F, Ohler R, Krugluger W, Reissner C, Lucas T, Brodowicz T, Roth E, Boltz-Nitulescu G (1997) Effects of 1 α,25-dihydroxyvitamin D3 and cytokines on the expression of MHC antigens, complement receptors and other antigens on human blood monocytes and U937 cells: role in cell differentiation, activation and phagocytosis. Immunology 90: 286–293

    Article  PubMed  CAS  Google Scholar 

  • Staeva-Vieira TP, Freedman LP (2002) 1,25-dihydroxyvitamin D3 inhibits IFN-γ and IL-4 levels during in vitro polarization of primary murine CD4+ T cells. J Immunol 168: 1181–1189

    PubMed  CAS  Google Scholar 

  • Stene LC, Joner G (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: 1128–1134

    PubMed  CAS  Google Scholar 

  • Szodoray P, Nakken B, Gaal J, Jonsson R, Szegedi A, Zold E, Szegedi G, Brun JG, Gesztelyi R, Zeher M, Bodolay E (2008) The complex role of vitamin D in autoimmune diseases. Scand J Immunol 68: 261–269

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi A, Reddy GS, Kobayashi T, Okano T, Park J, Sharma S (1998) Nuclear factor of activated T cells (NFAT) as a molecular target for 1α,25-dihydroxyvitamin D3-mediated effects. J Immunol 160: 209–218

    PubMed  CAS  Google Scholar 

  • Takiishi T, Gysemans C, Bouillon R, Mathieu C (2010) Vitamin D and diabetes. Endocrinol Metab Clin North Am 39: 419–446

    Article  PubMed  CAS  Google Scholar 

  • Thien R, Baier K, Pietschmann P, Peterlik M, Willheim M (2005) Interactions of 1 α,25-dihydroxyvitamin D3 with IL-12 and IL-4 on cytokine expression of human T lymphocytes. J Allergy Clin Immunol 116: 683–699

    Article  PubMed  CAS  Google Scholar 

  • Tsoukas CD, Provvedini DM, Manolagas SC (1984) 1,25-dihydroxyvitamin D3: a novel immunoregulatory hormone. Science 224: 1438–1440

    Article  PubMed  CAS  Google Scholar 

  • Ulitsky A, Ananthakrishnan AN, Naik A, Skaros S, Zadvornova Y, Binion DG, Issa M (2011) Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life. JPEN J Parenter Enteral Nutr 35: 308–316

    Article  PubMed  CAS  Google Scholar 

  • Unger WW, Laban S, Kleijwegt FS, van der Slik AR, Roep BO (2009) Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1. Eur J Immunol 39: 3147–3159

    Article  PubMed  CAS  Google Scholar 

  • Urry Z, Xystrakis E, Richards DF, McDonald J, Sattar Z, Cousins DJ, Corrigan CJ, Hickman E, Brown Z, Hawrylowicz CM (2009) Ligation of TLR9 induced on human IL-10-secreting Tregs by 1α,25-dihydroxyvitamin D3 abrogates regulatory function. J Clin Invest 119: 387–398

    PubMed  CAS  Google Scholar 

  • van Etten E, Mathieu CJ (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. Steroid Biochem Mol Biol 97: 93–101

    Article  CAS  Google Scholar 

  • Veldhoen M, Uyttenhove C, van Snick J, Helmby H, Westendorf A, Buer J, Martin B, Wilhelm C, Stockinger B (2008) Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 12: 1341–1346

    Article  CAS  Google Scholar 

  • Willheim M Thien R, Schrattbauer K, Bajna E, Holub M, Gruber R, Baier K, Pietschmann P, Reinisch W, Scheiner O, Peterlik M (1999) Regulatory effects of 1α,25-dihydroxyvitamin D3 on the cytokine production of human peripheral blood lymphocytes. J Clin Endocrinol Metab 84: 3739–3744

    Article  PubMed  CAS  Google Scholar 

  • Wong MT, Ye JJ, Alonso MN, Landrigan A, Cheung RK, Engleman E, Utz PJ (2010) Regulation of human Th9 differentiation by type I interferons and IL-21. Immunol Cell Biol 88: 624–631

    Article  PubMed  CAS  Google Scholar 

  • Workman CJ, Szymczak-Workman AL, Collison LW, Pillai MR, Vignali DA (2009) The development and function of regulatory T cells. Cell Mol Life Sci 66: 2603

    Article  PubMed  CAS  Google Scholar 

  • Xystrakis E, Kusumakar S, Boswell S, Peek E, Urry Z, Richards DF, Adikibi T, Pridgeon C, Dallman M, Loke TK, Robinson DS, Barrat FJ, O’Garra A, Lavender P, Lee TH, Corrigan C, Hawrylowicz CM (2006) Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J Clin Invest 116: 146–155

    Article  PubMed  CAS  Google Scholar 

  • Yu S, Cantorna MT (2008) The vitamin D receptor is required for iNKT cell development. Proc Natl Acad Sci U S A 105: 5207–5212

    Article  PubMed  CAS  Google Scholar 

  • Yu S, Cantorna MT (2011) Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice. J Immunol 186: 1384–1390

    Article  PubMed  CAS  Google Scholar 

  • Zarrabeitia MT, Riancho JA, Amado JA, Olmos JM, Gonzalez-Macias J (1992) Effect of calcitriol on the secretion of prostaglandin E2, interleukin 1, and tumor necrosis factor alpha by human monocytes. Bone 13: 185–189

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Immunology and Infectiology, Medical University of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Ursula Azizi-Semrad

  2. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Währinger Gürtel 18–20, 1090, Vienna, Austria

    Peter Pietschmann

  3. Department of Laboratory Medicine, Wilhelminenspital Vienna, Montleartstraße 37, 1160, Vienna, Austria

    Martin Willheim

Authors
  1. Ursula Azizi-Semrad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Peter Pietschmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Willheim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ursula Azizi-Semrad .

Editor information

Editors and Affiliations

  1. Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria

    Peter Pietschmann

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Wien NewYork

About this chapter

Cite this chapter

Azizi-Semrad, U., Pietschmann, P., Willheim, M. (2012). Effects of Vitamin D in the Immune System. In: Pietschmann, P. (eds) Principles of Osteoimmunology. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0520-7_4

Download citation

Publish with us

Policies and ethics

Search

Navigation