Converging pathways lead to overproduction of IL-17 in the absence of vitamin D signaling

Danny Bruce, Sanhong Yu, Jot Hui Ooi, Margherita T. Cantorna

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

Multiple pathways converge to result in the overexpression of Th17 cells in the absence of either vitamin D or the vitamin D receptor (VDR). CD4+ T cells from VDR knockout (KO) mice have a more activated phenotype than their wild-type (WT) counterparts and readily develop into Th17 cells under a variety of in vitro conditions. Vitamin D-deficient CD4+ T cells also overproduced IL-17 in vitro and 1,25 dihydroxyvitamin D3 inhibited the development of Th17 cells in CD4+ T-cell cultures. Conversely, the induction of inducible (i) Tregs was lower in VDR KO CD4+ T cells than WT and the VDR KO iTregs were refractory to IL-6 inhibition. Host-specific effects of the VDR were evident on in vivo development of naive T cells. Development of naive WT CD4+ T cells in the VDR KO host resulted in the overexpression of IL-17 and more severe experimental inflammatory bowel disease (IBD). The increased expression of Th17 cells in the VDR KO mice was associated with a reduction in tolerogenic CD103+ dendritic cells. The data collectively demonstrate that Th17 and iTreg cells are direct and indirect targets of vitamin D. The increased propensity for development of Th17 cells in the VDR KO host results in more severe IBD.

Original languageEnglish (US)
Pages (from-to)519-528
Number of pages10
JournalInternational immunology
Volume23
Issue number8
DOIs
StatePublished - Aug 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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