title: iRhom2 is required for the secretion of mouse TNFα.
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.
authors.affiliation: Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA. siggs@scripps.edu
authors.forename: Owen M
authors.initials: OM
authors.lastname: Siggs
authors.forename: Nengming
authors.initials: N
authors.lastname: Xiao
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hexin
authors.initials: H
authors.lastname: Shi
authors.forename: Wataru
authors.initials: W
authors.lastname: Tomisato
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Bruce
authors.initials: B
authors.lastname: Beutler
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005808:Genes, Recessive / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C569468:iRhom2 protein, mouse