Immunomodulatory effects of vitamin D: implications for GVHD.
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.
Rosenblatt
J
J
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. jrosenb1@bidmc.harvard.edu
Bissonnette
A
A
Ahmad
R
R
Wu
Z
Z
Vasir
B
B
Stevenson
K
K
Zarwan
C
C
Keefe
W
W
Glotzbecker
B
B
Mills
H
H
Joyce
R
R
Levine
J D
JD
Tzachanis
D
D
Boussiotis
V
V
Kufe
D
D
Avigan
D
D
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*
D007155:Immunologic Factors; D008934:Mitogens; D014807:Vitamin D