Open AccessImmunomodulatory effects of vitamin D: implications for GVHD
Author(s) -
Jacalyn Rosenblatt,
Adam Bissonnette,
Rehan Ahmad,
Zhiyou Wu,
Baldev Vasir,
Kristen E. Stevenson,
Corrine Zarwan,
Whitney Keefe,
Brett Glotzbecker,
Heidi Mills,
Robin Joyce,
James D. Levine,
D. Tzachanis,
Viki A. Boussiotis,
Donald Küfe,
David Avigan
Publication year - 2010
Publication title -
bone marrow transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.609
H-Index - 127
eISSN - 1476-5365
pISSN - 0268-3369
DOI - 10.1038/bmt.2009.366
Subject(s) - vitamin d and neurology , t cell , immunology , medicine , immune system , haematopoiesis , graft versus host disease , transplantation , vitamin d deficiency , vitamin , stimulation , downregulation and upregulation , endocrinology , biology , stem cell , microbiology and biotechnology , biochemistry , gene
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.