iRhom2 and TNF: Partners or enemies?

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Science Signaling  29 Oct 2019:
Vol. 12, Issue 605, eaaz0444
DOI: 10.1126/scisignal.aaz0444


  • Fig. 1 Mechanism by which iRhom2 attenuates HSC activation and fibrogenesis.

    During liver injury, Kupffer cells, monocyte-derived macrophages, or hepatocytes secrete inflammatory cytokines, including TNF-α. The resulting inflammatory environment leads to an increase in the amounts of iRhom2 in hepatic stellate cells (HSCs), increasing ADAM17 activity and leading to the cleavage of TNFR2. This allows the latter to act as a soluble decoy to sequester TNF-α, thus preventing TNFR1 signaling. In the absence of this iRhom2-dependent inhibitory mechanism, TNF-α binds to TNFR1 to promote HSC proliferation and activation to become myofibroblasts, leading to fibrosis.


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