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- Title
T-bet over-expression regulates aryl hydrocarbon receptor-mediated T helper type 17 differentiation through an interferon (IFN)γ-independent pathway.
- Authors
Yokosawa, M.; Kondo, Y.; Tahara, M.; Iizuka‐Koga, M.; Segawa, S.; Kaneko, S.; Tsuboi, H.; Yoh, K.; Takahashi, S.; Matsumoto, I.; Sumida, T.
- Abstract
Various transcription factors are also known to enhance or suppress T helper type 17 (Th17) differentiation. We have shown previously that the development of collagen-induced arthritis was suppressed in T-bet transgenic (T-bet Tg) mice, and T-bet seemed to suppress Th17 differentiation through an interferon (IFN)-γ-independent pathway, although the precise mechanism remains to be clarified. The present study was designed to investigate further the mechanisms involved in the regulation of Th17 differentiation by T-bet over-expression, and we found the new relationship between T-bet and aryl hydrocarbon receptor (AHR). Both T-bet Tg mice and IFN-γ-/--over-expressing T-bet (T-bet Tg/IFN-γ-/-) mice showed inhibition of retinoic acid-related orphan receptor (ROR)γt expression and IL-17 production by CD4+ T cells cultured under conditions that promote Th-17 differentiation, and decreased IL-6 receptor (IL-6R) expression and signal transducer and activator of transcription-3 (STAT-3) phosphorylation in CD4+ T cells. The mRNA expression of ahr and rorc were suppressed in CD4+ T cells cultured under Th-17 conditions from T-bet Tg mice and T-bet Tg/IFN-γ-/- mice. CD4+ T cells of wild-type (WT) and IFN-γ-/- mice transduced with T-bet-expressing retrovirus also showed inhibition of IL-17 production, whereas T-bet transduction had no effect on IL-6R expression and STAT-3 phosphorylation. Interestingly, the mRNA expression of ahr and rorc were suppressed in CD4+ T cells with T-bet transduction cultured under Th17 conditions. The enhancement of interleukin (IL)−17 production from CD4+ T cells by the addition of AHR ligand with Th17 conditions was cancelled by T-bet over-expression. Our findings suggest that T-bet over-expression-induced suppression of Th17 differentiation is mediated through IFN-γ-independent AHR suppression.
- Subjects
GENETIC transcription; T helper cells; ARTHRITIS; PHOSPHORYLATION; CELLULAR signal transduction
- Publication
Clinical & Experimental Immunology, 2017, Vol 188, Issue 1, p22
- ISSN
0009-9104
- Publication type
Article
- DOI
10.1111/cei.12912