Distinct roles of T-bet and STAT4 in suppression of IL-4-producing potential in Th1 cells by IFN-γ signaling

Chunxian Du; Yonggang Kong; Pengchao Hu; Hui Song; Jingyi Fan; Fang Yang

doi:10.5114/ceji.2013.39762

eISSN: 1644-4124
ISSN: 1426-3912

Central European Journal of Immunology

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4/2013
vol. 38

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abstract:

Distinct roles of T-bet and STAT4 in suppression of IL-4-producing potential in Th1 cells by IFN-γ signaling

Chunxian Du

,

Yonggang Kong

,

Pengchao Hu

,

Hui Song

,

Jingyi Fan

,

Fang Yang

(Centr Eur J Immunol 2013; 38 (4): 461-469)

DOI: https://doi.org/10.5114/ceji.2013.39762

Online publish date: 2013/12/30

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Previously, we reported that signal transducers and activators of transcription (STAT)-1 was required for optimal Th1 cell differentiation. T-bet is the master regulator and STAT1 promotes Th1 cells partly through upregulating T-bet and interferon γ(IFN-γ). However, the mechanism that leads to silence of interleukin (IL)-4 expression in Th1 cells has not been fully understood. In this study, we further dissected signaling pathways that contribute to repression of IL-4-producing potential in Th1 cells. We showed that blockage of IFN-γ signaling resulted in failure to suppress IL-4-producing potential. Consistently, IFN-γ efficiently antagonized IL-4 signaling while IL-12 failed to do so, suggesting that IL-12/STAT4 signaling might not be required for IFN-γ-mediated function. To support this, we discovered that IFN-γ signaling inhibited IL-4-producing potential in STAT4-deficient CD4+ T cells. On the other hand, T-bet deficiency abrogated IFN-γ-mediated suppression of IL-4-producing potential. These observations suggest that T-bet but not STAT4 is required for IFN-γ-mediated suppression of IL-4-producing potential.

keywords:

Distinct roles of T-bet and STAT4 in suppression of IL-4-producing potential in Th1 cells by IFN-γ signaling

Chunxian Du , Yonggang Kong , Pengchao Hu , Hui Song , Jingyi Fan , Fang Yang

cytokines, Th1 cells, signal transduction

Chunxian Du

,

Yonggang Kong

,

Pengchao Hu

,

Hui Song

,

Jingyi Fan

,

Fang Yang