iRhom2 is required for the secretion of mouse TNFα.

Journal article

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.

Authors: Siggs, O; Xiao, N; Wang, Y; Shi, H; Tomisato, W

• Journal: Blood
• Volume: 119
• Issue: 24
• Pages: 5769-5771
• Publication date: 2012-06-01
• DOI: 10.1182/blood-2012-03-417949
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Toll-Like Receptors; Alleles; Mutation; Base Sequence; Mice, Inbred C57BL; Carrier Proteins; Animals; DNA Mutational Analysis; Tumor Necrosis Factor-alpha; Genes, Recessive; Mice; Molecular Sequence Data