TAM receptors are pleiotropic inhibitors of the innate immune response.

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234

作者：

CV Rothlin，S Ghosh，EI Zuniga，M Oldstone，G Lemke

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摘要：

The activation of Toll-like receptors (TLRs) in dendritic cells (DCs) triggers a rapid inflammatory response to pathogens. However, this response must be tightly regulated because unrestrained TLR signaling generates a chronic inflammatory milieu that often leads to autoimmunity. We have found that the TAM receptor tyrosine kinases—Tyro3, Axl, and Mer—broadly inhibit both TLR and TLR-induced cytokine-receptor cascades. Remarkably, TAM inhibition of inflammation is transduced through an essential stimulator of inflammation—the type I interferon receptor (IFNAR)—and its associated transcription factor STAT1. TLR induction of IFNAR-STAT1 signaling upregulates the TAM system, which in turn usurps the IFNAR-STAT1 cassette to induce the cytokine and TLR suppressors SOCS1 and SOCS3. These results illuminate a self-regulating cycle of inflammation, in which the obligatory, cytokine-dependent activation of TAM signaling hijacks a proinflammatory pathway to provide an intrinsic feedback inhibitor of both TLR- and cytokine-driven immune responses.

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关键词：

CELLIMMUNO MOLIMMUNO

DOI：

10.1016/j.cell.2007.10.034

被引量：

1228

年份：

2007