{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:16:10Z","timestamp":1790223370550,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,1,6]],"date-time":"2025-01-06T00:00:00Z","timestamp":1736121600000},"content-version":"vor","delay-in-days":2684,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["immunohorizons.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>IL-17 activates NF-\u03baB and induces expression of proinflammatory genes. IL-17 drives disease in autoimmune conditions, and anti\u2013IL-17 Abs have shown impressive success in the clinic. Although produced by lymphocytes, IL-17 predominantly signals in fibroblasts and epithelial cells. IL-17\u2013driven inflammation is kept in check by negative feedback signaling molecules, including the ubiquitin editing enzyme A20, whose gene TNFAIP3 is linked to autoimmune disease susceptibility. The A20 binding inhibitor of NF-\u03baB activation 1 (ABIN-1) is an A20-binding protein encoded by the TNIP1 gene, which is also linked to autoimmune disease susceptibility including psoriasis. Accordingly, we hypothesized that ABIN-1 might play a role in negatively regulating IL-17 signaling activity. Indeed, ABIN-1 enhanced both tonic and IL-17\u2013dependent NF-\u03baB signaling in IL-17\u2013responsive fibroblast cells. Interestingly, the inhibitory activities of ABIN-1 on IL-17 signaling were independent of A20. ABIN-1 is a known NF-\u03baB target gene, and we found that IL-17\u2013induced activation of NF-\u03baB led to enhanced ABIN-1 mRNA expression and promoter activity. Surprisingly, however, the ABIN-1 protein was inducibly degraded following IL-17 signaling in a proteasome-dependent manner. Thus, ABIN-1, acting independently of A20, restricts both baseline and IL-17\u2013induced inflammatory gene expression. We conclude that IL-17\u2013induced signals lead to degradation of ABIN-1, thereby releasing a constitutive cellular brake on NF-\u03baB activation.<\/jats:p>","DOI":"10.4049\/immunohorizons.1700035","type":"journal-article","created":{"date-parts":[[2017,9,2]],"date-time":"2017-09-02T00:40:18Z","timestamp":1504312818000},"page":"133-141","update-policy":"https:\/\/doi.org\/10.4049\/immunohorizon.f110.005975","source":"Crossref","is-referenced-by-count":29,"title":["IL-17 Signaling Triggers Degradation of the Constitutive NF-\u03baB Inhibitor ABIN-1"],"prefix":"10.1093","volume":"1","author":[{"given":"J Agustin","family":"Cruz","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E","family":"Childs","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7942-1742","authenticated-orcid":false,"given":"Nilesh","family":"Amatya","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek V","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-582X","authenticated-orcid":false,"given":"Rudi","family":"Beyaert","sequence":"additional","affiliation":[{"name":"VIB-UGent Center for Inflammation Research , Zwijnaarde, Ghent 9052 ,","place":["Belgium"]},{"name":"Department of Biomedical Molecular Biology, Ghent University , Zwijnaarde, Ghent 9052 ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-516X","authenticated-orcid":false,"given":"Lawrence P","family":"Kane","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J","family":"Aneskievich","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut , Storrs, CT 06269"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Averil","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California , San Francisco, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah L","family":"Gaffen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"},{"name":"Department of Immunology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2025010608404783200_r1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.4049\/jimmunol.1500909","article-title":"IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans","volume":"195","author":"Conti","year":"2015","journal-title":"J. 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