STAT6 and Furin Are Successive Triggers for the Production of TGF-β by T Cells.

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 is necessary and sufficient for the expression of TGF-β propeptide in T cells. duanyu18136 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 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 duanyu18136 and furin.

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