title: Immunomodulatory effects of vitamin D: implications for GVHD.
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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jrosenb1@bidmc.harvard.edu
authors.forename: J
authors.initials: J
authors.lastname: Rosenblatt
authors.forename: A
authors.initials: A
authors.lastname: Bissonnette
authors.forename: R
authors.initials: R
authors.lastname: Ahmad
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: B
authors.initials: B
authors.lastname: Vasir
authors.forename: K
authors.initials: K
authors.lastname: Stevenson
authors.forename: C
authors.initials: C
authors.lastname: Zarwan
authors.forename: W
authors.initials: W
authors.lastname: Keefe
authors.forename: B
authors.initials: B
authors.lastname: Glotzbecker
authors.forename: H
authors.initials: H
authors.lastname: Mills
authors.forename: R
authors.initials: R
authors.lastname: Joyce
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
authors.forename: D
authors.initials: D
authors.lastname: Tzachanis
authors.forename: V
authors.initials: V
authors.lastname: Boussiotis
authors.forename: D
authors.initials: D
authors.lastname: Kufe
authors.forename: D
authors.initials: D
authors.lastname: Avigan
mesh_terms: D016764:Cell Polarity / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016130:Immunophenotyping; D008934:Mitogens / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D014807:Vitamin D / Q000494:pharmacology*
chemical_list: D007155:Immunologic Factors; D008934:Mitogens; D014807:Vitamin D