Li, YueLiu, WeirenGuan, XiaqunTruscott, JamieCreemers, John W.Chen, Hung-LinPesu, MarkoEl Abiad, Rami G.Karacay, BahriUrban, Joseph F.Elliott, David E.Kaplan, Mark H.Blazar, Bruce R.Ince, M. Nedim2020-01-092020-01-092018-11Li, Y., Liu, W., Guan, X., Truscott, J., Creemers, J. W., Chen, H. L., … Ince, M. N. (2018). STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells. Journal of immunology (Baltimore, Md. : 1950), 201(9), 2612–2623. doi:10.4049/jimmunol.1700808https://hdl.handle.net/1805/21805Production 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.en-USPublisher PolicyFurinGraft vs Host DiseaseSTAT6 Transcription FactorStrongylida InfectionsT-LymphocytesTransforming Growth Factor betaArticle