The paradoxical effects of vitamin D on type 1 mediated immunity

Abstract

Low vitamin D status is associated with an increased risk of Th1 mediated autoimmune diseases like inflammatory bowel disease. 1,25(OH)(2)D(3) treatments have been shown to suppress Th1 mediated immunity and protect animals from experimental autoimmunity. Th1 mediated immunity is important for clearance of a number of different infectious diseases. For tuberculosis 1,25(OH)(2)D(3) treatment is associated with decreased Th1 mediated immunity but increased bactericidal activity. Systemic candidiasis is unaffected by 1,25(OH)(2)D(3) treatment. The seemingly paradoxical effects of 1,25(OH)(2)D(3) and vitamin D on Th1 mediated autoimmunity versus infectious immunity point to a broad array of vitamin D targets in the immune system. The interplay of these vitamin D targets and their impact on the host-immune response then dictate the outcome.

Fig. 1

CD4+ T helper cell subsets and functions. The black arrows (→) indicate cytokines that induce differentiation and the black lines ( ) indicate cytokines that inhibit Th cell development. The grey arrows and lines indicate induction ( ) or suppression ( ) by 1,25(OH)₂D₃ treatment. Th1 immune responses are inhibited by Th2 and T reg cells and are important for protection from intracellular infections, cancer immunity and participate in autoimmune disease. Th2 cell immune responses are also important for fighting infections, can be suppressed by T reg cells and are pathogenic in asthma and allergies. Regulatory NKT cells can be either pathogenic or protective for autoimmune responses and are required for experimental asthma disease induction. All T cells that have been tested express the VDR. 1,25(OH)₂D₃ suppresses Th1 driven cytokine responses, induces T reg cells, induces IL-4 production and enhances NKT cell function.

Fig. 2

Model of the effects of vitamin D status and 1,25(OH)₂D₃ treatment on Chron’s disease. When vitamin D is low NKT cells and T reg cells fail to develop, Th1 cells are overactive and the incidence of Th1 mediated diseases increase. Vitamin D regulates the APC such that Th1 cell responses are inhibited, T reg cell function is induced and NKT cells develop. The net result is decreased Chron’s disease and normalization of the Th cell response.