T‐bet regulates differentiation of forkhead box protein 3+ regulatory T cells in programmed cell death‐1‐deficient mice |
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| Authors: | M. Tahara Y. Kondo M. Yokosawa H. Tsuboi S. Takahashi S. Shibayama I. Matsumoto T. Sumida |
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| Affiliation: | 1. Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan;2. Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan;3. Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan;4. Tsukuba Institute ONO Pharmaceutical Co., LTD., Tsukuba, Ibaraki, Japan |
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| Abstract: | Programmed cell death‐1 (PD‐1) plays an important role in peripheral T cell tolerance, but whether or not it affects the differentiation of helper T cell subsets remains elusive. Here we describe the importance of PD‐1 in the control of T helper type 1 (Th1) cell activation and development of forkhead box protein 3 (FoxP3+) regulatory T cells (Tregs). PD‐1‐deficient T cell‐specific T‐bet transgenic (P/T) mice showed growth retardation, and the majority died within 10 weeks. P/T mice showed T‐bet over‐expression, increased interferon (IFN)‐γ production by CD4+ T cells and significantly low FoxP3+ Treg cell percentage. P/T mice developed systemic inflammation, which was probably induced by augmented Th1 response and low FoxP3+ Treg count. The study identified a unique, previously undescribed role for PD‐1 in Th1 and Treg differentiation, with potential implication in the development of Th1 cell‐targeted therapy. |
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| Keywords: | FoxP3+ regulatory T cells helper T cell subsets programmed cell death‐1 T cell tolerance Th1 cells |
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