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Yue Li, Weiren Liu, Xiaqun Guan, Jamie Truscott, John W Creemers, Hung-Lin Chen, Marko Pesu, Rami G El Abiad, Bahri Karacay, Joseph F Urban, David E Elliott, Mark H Kaplan, Bruce R Blazar, M Nedim Ince, STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells, The Journal of Immunology, Volume 201, Issue 9, November 2018, Pages 2612–2623, https://doi.org/10.4049/jimmunol.1700808
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Abstract
Production of TGF-β by T cells is key to various aspects of immune homeostasis, with defects in this process causing or aggravating immune-mediated disorders. The molecular mechanisms that lead to TGF-β generation by T cells remain largely unknown. To address this issue, we take advantage of the fact that intestinal helminths stimulate Th2 cells besides triggering TGF-β generation by T lymphocytes and regulate immune-mediated disorders. We show that the Th2 cell–inducing transcription factor STAT6 is necessary and sufficient for the expression of TGF-β propeptide in T cells. STAT6 is also necessary for several helminth-triggered events in mice, such as TGF-β–dependent suppression of alloreactive inflammation in graft-versus-host disease. Besides STAT6, helminth-induced secretion of active TGF-β requires cleavage of propeptide by the endopeptidase furin. Thus, for the immune regulatory pathway necessary for TGF-β production by T cells, our results support a two-step model, composed of STAT6 and furin.