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iRhom2 is required for the secretion of mouse TNFα

2012; Elsevier BV; Volume: 119; Issue: 24 Linguagem: Inglês

10.1182/blood-2012-03-417949

1528-0020

Owen M. Siggs, Nengming Xiao, Ying Wang, Hexin Shi, Wataru Tomisato, Xiaohong Li, Yu Xia, Bruce Beutler,

NF-κB Signaling Pathways

Abstract TNFα is a powerful inflammatory stimulus, central both to the control of infection, and as an agent of inflammatory disease. The most potent inducers of TNFα secretion signal through the Toll-like receptors, and we describe here a chemically-induced mutation that impairs this response in macrophages. A missense mutation was revealed in the gene encoding the inactive rhomboid protease iRhom2, which was not complemented by a null allele of the same gene. Neither the missense nor the null allele affected TLR-induced secretion of IL-6. Moreover, unlike a mutation in TNFα, the iRhom2 missense mutation did not cause enhanced susceptibility to colitis induced by dextran sodium sulfate. These results establish a specific role for iRhom2 in the secretion of TNFα, and present a new target for the modulation of inflammation.