| First Author | Rothlin CV | Year | 2007 |
| Journal | Cell | Volume | 131 |
| Issue | 6 | Pages | 1124-36 |
| PubMed ID | 18083102 | Mgi Jnum | J:131447 |
| Mgi Id | MGI:3773763 | Doi | 10.1016/j.cell.2007.10.034 |
| Citation | Rothlin CV, et al. (2007) TAM receptors are pleiotropic inhibitors of the innate immune response. Cell 131(6):1124-36 |
| abstractText | 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. |
