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Studies on overcoming such resistance would provide a novel treatment strategy for RA in a clinical setting.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>IL13R\u03b11 expression was assessed in the synovial tissue by RT-qPCR, immunohistology, and Western blot. Gain or loss of functional analysis was applied to evaluate the biological roles of IL13R\u03b11 in RA FLSs. Cell viability and apoptosis were assessed by MTS, Western blot, and flow cytometry. The therapeutic effects of IL13R\u03b11 on the severity of type II collagen-induced arthritis (CIA) in DBA-\/1 mouse model were evaluated by scoring synovitis, hyperplasia, cartilage degradation, and bone destruction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>IL13R\u03b11 expression was selectively downregulated when RA FLSs were stimulated by ER stress inducers. Functionally, IL13R\u03b11 overexpression could inhibit the viability, but induce the apoptosis of RA FLSs in the presence of ER stress inducers. Mechanistically, IL13R\u03b11 promotes cell apoptosis via transcriptionally activating trail expression. Besides, IL13R\u03b11 could interact and stabilize DR5 protein, thus forming a positive loop involving trail and DR5 to render RA FLSs more susceptible to apoptosis. Additionally, intraarticular injection of IL13R\u03b11 conferred therapeutic effects in CIA models and showed a limited degree of synovial proliferation and joint destruction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Together, our data establishes a regulatory role for IL13R\u03b11 to combat the apoptotic resistance of RA FLSs against ER stress. The inhibitory effects of IL13R\u03b11 on arthritis progression suggest the therapeutic potential in RA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13075-020-02270-4","type":"journal-article","created":{"date-parts":[[2020,8,8]],"date-time":"2020-08-08T08:03:36Z","timestamp":1596873816000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["IL13R\u03b11 protects against rheumatoid arthritis by combating the apoptotic resistance of fibroblast-like synoviocytes"],"prefix":"10.1186","volume":"22","author":[{"given":"Xiaomei","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luna","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kehong","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhua","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengfang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,8]]},"reference":[{"key":"2270_CR1","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.tips.2018.03.010","volume":"39","author":"M Rahmati","year":"2018","unstructured":"Rahmati M, Moosavi MA, McDermott MF. 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Tissues were collected during knee replacement surgery from patients with RA and OA. Participants provided written informed consent to participate in the study and to allow their biological samples to be genetically analyzed. The Ethical Committee of the Shandong Academy of Medical Sciences approved this study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"184"}}