Vitamin D signaling in immune-mediated disorders: Evolving insights and therapeutic opportunities.
1,25(OH)(2)D(3), the active form of vitamin D, is a central player in calcium and bone metabolism. More recently, important immunomodulatory effects have been attributed to this hormone. The widespread presence of the vitamin D receptor (VDR) in the immune system and the expression of the enzymes responsible for the synthesis of the active 1,25(OH)(2)D(3) regulated by specific immune signals, even suggest a paracrine immunomodulatory role for 1,25(OH)(2)D(3). Additionally, the different molecular mechanisms used by 1,25(OH)(2)D(3) to exert its immunomodulatory effects prove of a broad action radius for this compound. Both, the effects of vitamin D deficiency and/or absence of the VDR as well as intervention with pharmacological doses of 1,25(OH)(2)D(3) or one of its less-calcemic analogs, affects immune system behavior in different animal models of immune-mediated disorders, such as type 1 diabetes. This review aims to summarize the data as they stand at the present time on the role of vitamin D in the pathogenesis of immune-mediated disorders, with special focus on type 1 diabetes, and on the therapeutic opportunities for vitamin D in the prevention and treatment of this autoimmune disease in mouse models and humans.
Baeke
Femke
F
Laboratory for Experimental Medicine and Endocrinology (Legendo), Katholieke Universiteit Leuven, Leuven, Belgium.
van Etten
Evelyne
E
Gysemans
Conny
C
Overbergh
Lut
L
Mathieu
Chantal
C
D000818:Animals; D004195:Disease Models, Animal; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use
D006728:Hormones; D014807:Vitamin D