Immunomodulatory effects of vitamin D: implications for GVHD
J Rosenblatt, A Bissonnette, R Ahmad, Z Wu, B Vasir, K Stevenson, C Zarwan, W Keefe, B Glotzbecker, H Mills, R Joyce, J D Levine, D Tzachanis, V Boussiotis, D Kufe, D Avigan, J Rosenblatt, A Bissonnette, R Ahmad, Z Wu, B Vasir, K Stevenson, C Zarwan, W Keefe, B Glotzbecker, H Mills, R Joyce, J D Levine, D Tzachanis, V Boussiotis, D Kufe, D Avigan
Abstract
GVHD remains a major source of morbidity and mortality after allogeneic BMT. GVHD is mediated by alloreactive T cells derived from the hematopoietic graft that target host tissues. Pre-clinical models have shown that presentation of alloantigens by host DCs results in the activation of donor-derived T cells that mediate GVHD. Strategies that interfere with the Ag-presenting capacity of DCs after allogeneic transplantation may decrease the risk of developing GVHD. Vitamin D is a hormone essential for calcium metabolism that shows immunomodulatory properties. We showed that correction of vitamin D deficiency appeared to mitigate manifestations of GVHD. In pre-clinical studies, we have shown that vitamin D inhibits DC maturation, polarizes T-cell populations toward the expression of Th2 as compared with Th1 cytokines, and blunts allogeneic T-cell proliferation in response to DC stimulation. Exposure to vitamin D resulted in increased expression of IDO, an enzyme responsible for tryptophan metabolism that is upregulated in tolerizing DCs. These data suggest that exposure to vitamin D results in immature DC populations that bias toward tolerizing rather than stimulatory T-cell populations. Vitamin D may therefore have a role in the prevention of GVHD.
Conflict of interest statement
Conflict of interest
The authors declare no conflict of interest.
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Source: PubMed