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

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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 2012

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Calcitriol Receptors
Up-Regulation
T-Lymphocytes
Vitamin D Deficiency
Graft vs Host Disease
Vitamin D
Stem Cells
Transplants
Phosphorylation
Cytokines
Inflammation
Incidence

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Joseph, R. W., Bayraktar, U. D., Kim, T. K., John, S. L. S., Popat, U., Khalili, J., ... 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

Vitamin D receptor upregulation in alloreactive human T cells. / Joseph, Richard W; Bayraktar, Ulas D.; Kim, Tae Kon; John, St Lisa S; Popat, Uday; Khalili, Jahan; Molldrem, Jeffrey J.; Wieder, Eric D.; Komanduri, Krishna V.

In: Human Immunology, Vol. 73, No. 7, 07.2012, p. 693-698.

Research output: Contribution to journalArticle

Joseph, RW, Bayraktar, UD, Kim, TK, John, SLS, Popat, U, Khalili, J, Molldrem, JJ, Wieder, ED & Komanduri, KV 2012, 'Vitamin D receptor upregulation in alloreactive human T cells', Human Immunology, vol. 73, no. 7, pp. 693-698. https://doi.org/10.1016/j.humimm.2012.04.019
Joseph RW, Bayraktar UD, Kim TK, John SLS, Popat U, Khalili J et al. Vitamin D receptor upregulation in alloreactive human T cells. Human Immunology. 2012 Jul;73(7):693-698. https://doi.org/10.1016/j.humimm.2012.04.019
Joseph, Richard W ; Bayraktar, Ulas D. ; Kim, Tae Kon ; John, St Lisa S ; Popat, Uday ; Khalili, Jahan ; Molldrem, Jeffrey J. ; Wieder, Eric D. ; Komanduri, Krishna V. / Vitamin D receptor upregulation in alloreactive human T cells. In: Human Immunology. 2012 ; Vol. 73, No. 7. pp. 693-698.
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