title: Vitamin D receptor upregulation in alloreactive human T cells.
abstract: Vitamin D deficiency is adversely associated with diseases characterized by inflammation. The combination of the high incidence of vitamin D deficiency in patients undergoing allogeneic stem cell transplants (SCT) and the potential role of vitamin D deficiency in influencing graft-versus-host disease led us to further characterize the expression of VDR on alloreactive T cells. We hypothesized that vitamin D receptor expression may directly regulate alloreactive T cell responses. To overcome existing limitations in measuring VDR in bulk cellular populations, we developed a flow cytometric assay to measure cytoplasmic VDR in human T cells. Upon stimulation, VDR was expressed extremely early and exhibited sustained upregulation with chronic stimulation. VDR expression was also coupled to cytokine production, proliferation, and ERK1/2 phosphorylation. In addition, VDR exhibited a maturation stage-specific pattern of expression, with greatest expression on cells known to mediate GVHD, naïve and early memory T cells. Alloreactive T cells upregulated VDR, whereas the nonreactive T cells did not. Finally, repletion of vitamin D in vitro was sufficient to significantly reduce alloreactive T cell responses. These data suggest that vitamin D effects on T cells may be important in reducing graft versus host disease (GVHD) in the allogeneic stem cell transplant setting.
authors.affiliation: Division of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Joseph
authors.forename: Ulas D
authors.initials: UD
authors.lastname: Bayraktar
authors.forename: Tae Kon
authors.initials: TK
authors.lastname: Kim
authors.forename: Lisa S
authors.initials: LS
authors.lastname: St John
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.forename: Jahan
authors.initials: J
authors.lastname: Khalili
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Molldrem
authors.forename: Eric D
authors.initials: ED
authors.lastname: Wieder
authors.forename: Krishna V
authors.initials: KV
authors.lastname: Komanduri
mesh_terms: D002454:Cell Differentiation; D002469:Cell Separation; D002478:Cells, Cultured; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D056747:Immunomodulation; D007519:Isoantigens / Q000276:immunology; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation; D014807:Vitamin D / Q000378:metabolism
chemical_list: D007519:Isoantigens; D018167:Receptors, Calcitriol; D014807:Vitamin D