Vitamin D receptor upregulation in alloreactive human T cells

Richard W. Joseph, Ulas D. Bayraktar, Tae Kon Kim, St Lisa S. John, Uday Popat, Jahan Khalili, Jeffrey J. Molldrem, Eric D. Wieder, Krishna V. Komanduri

Research output: Contribution to journalArticle

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)693-698
Number of pages6
JournalHuman Immunology
Volume73
Issue number7
DOIs
StatePublished - Jul 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Joseph, R. W., Bayraktar, U. D., Kim, T. K., John, S. L. S., Popat, U., Khalili, J., Molldrem, J. J., Wieder, E. D., & Komanduri, K. V. (2012). Vitamin D receptor upregulation in alloreactive human T cells. Human Immunology, 73(7), 693-698. https://doi.org/10.1016/j.humimm.2012.04.019