{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Issuree PD"],"funding":["NIDCR NIH HHS","NCI NIH HHS","NIAMS NIH HHS","NIGMS NIH HHS","PHS HHS"],"pagination":["928-32"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3561822"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["123(2)"],"pubmed_abstract":["iRHOM2, encoded by the gene Rhbdf2, regulates the maturation of the TNF-α convertase (TACE), which controls shedding of TNF-α and its biological activity in vivo. TACE is a potential target to treat TNF-α-dependent diseases, such as rheumatoid arthritis, but there are concerns about potential side effects, because TACE also protects the skin and intestinal barrier by activating EGFR signaling. Here we report that inactivation of Rhbdf2 allows tissue-specific regulation of TACE by selectively preventing its maturation in immune cells, without affecting its homeostatic functions in other tissues. The related iRHOM1, which is widely expressed, except in hematopoietic cells, supported TACE maturation and shedding of the EGFR ligand TGF-α in Rhbdf2-deficient cells. Remarkably, mice lacking Rhbd"],"journal":["The Journal of clinical investigation"],"pubmed_title":["iRHOM2 is a critical pathogenic mediator of inflammatory arthritis."],"pmcid":["PMC3561822"],"funding_grant_id":["R01 AR038889","R01 GM064750","P30 CA008748","AR38889","R01 AR046713","LA2558/3-1","AR050401","K99 AR061430","R01 DE019420","R01 AR050401","AR061430","R01 GM64750","R00 AR061430","R55 AR038889"],"pubmed_authors":["Yarilina A","Mak TW","Kalliolias GD","Ivashkiv LB","Monette S","Horiuchi K","Swendeman SL","Maretzky T","Park-Min KH","Binder N","Qing X","Blobel CP","Issuree PD","Salmon JE","McIlwain DR","Lang PA"],"additional_accession":[]},"is_claimable":false,"name":"iRHOM2 is a critical pathogenic mediator of inflammatory arthritis.","description":"iRHOM2, encoded by the gene Rhbdf2, regulates the maturation of the TNF-α convertase (TACE), which controls shedding of TNF-α and its biological activity in vivo. TACE is a potential target to treat TNF-α-dependent diseases, such as rheumatoid arthritis, but there are concerns about potential side effects, because TACE also protects the skin and intestinal barrier by activating EGFR signaling. Here we report that inactivation of Rhbdf2 allows tissue-specific regulation of TACE by selectively preventing its maturation in immune cells, without affecting its homeostatic functions in other tissues. The related iRHOM1, which is widely expressed, except in hematopoietic cells, supported TACE maturation and shedding of the EGFR ligand TGF-α in Rhbdf2-deficient cells. Remarkably, mice lacking Rhbd","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Feb","modification":"2025-04-19T12:18:40.435Z","creation":"2019-03-27T01:04:12Z"},"accession":"S-EPMC3561822","cross_references":{"pubmed":["23348744"],"doi":["10.1172/jci66168","10.1172/JCI66168"]}}