Browsing by Author "Pesu, Marko"

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    STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells
    (The American Association of Immunologists, Inc., 2018-11) Li, Yue; Liu, Weiren; Guan, Xiaqun; Truscott, Jamie; Creemers, John W.; Chen, Hung-Lin; Pesu, Marko; El Abiad, Rami G.; Karacay, Bahri; Urban, Joseph F.; Elliott, David E.; Kaplan, Mark H.; Blazar, Bruce R.; Ince, M. Nedim; Pediatrics, School of Medicine
    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.