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IL-1R1 is the receptor for IL-1, and IL-1R2 is suggested to be a decoy receptor, because it lacks the signal-transducing TIR domain in the cytoplasmic part. However, the roles of IL-1R2 in health and disease remain largely unknown. In this study, we generated EGFP-knock-in Il1r2\u2212\/\u2212 mice and showed that they were highly susceptible to collagen-induced arthritis, an animal model for rheumatoid arthritis in which the expression of IL-1R2 is augmented in inflammatory joints. Il1r2 was highly expressed in neutrophils but had only low expression in other cells, including monocytes and macrophages. Ab production and T cell responses against type II collagen were normal in Il1r2\u2212\/\u2212 mice. Despite the high expression in neutrophils, no effects of Il1r2 deficiency were observed; however, we found that production of inflammatory mediators in response to IL-1 was greatly enhanced in Il1r2\u2212\/\u2212 macrophages. These results suggest that IL-1R2 is an important regulator of arthritis by acting specifically on macrophages as a decoy receptor for IL-1.<\/jats:p>","DOI":"10.4049\/jimmunol.1402155","type":"journal-article","created":{"date-parts":[[2015,2,28]],"date-time":"2015-02-28T03:52:41Z","timestamp":1425095561000},"page":"3156-3168","source":"Crossref","is-referenced-by-count":83,"title":["IL-1 Receptor Type 2 Suppresses Collagen-Induced Arthritis by Inhibiting IL-1 Signal on Macrophages"],"prefix":"10.1093","volume":"194","author":[{"given":"Kenji","family":"Shimizu","sequence":"first","affiliation":[{"name":"Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science , Chiba 278-0022 ,","place":["Japan"]},{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuko","family":"Sudo","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuhiko","family":"Mizoroki","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuro","family":"Ikarashi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiko","family":"Horai","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Kakuta","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]},{"name":"Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo , Tokyo 113-8657 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoichiro","family":"Iwakura","sequence":"additional","affiliation":[{"name":"Center for Animal Disease Models, Research Institute for Biomedical Sciences, Tokyo University of Science , Chiba 278-0022 ,","place":["Japan"]},{"name":"Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo , Tokyo 108-8639 ,","place":["Japan"]},{"name":"Core Research for Evolutional Science and Technology, Japan Science and Technology Agency , Saitama 332-0012 ,","place":["Japan"]},{"name":"Medical Mycology Research Center, Chiba University , Chiba 250-8673 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,4,1]]},"reference":[{"key":"2025030705361892900_r1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"Dinarello","year":"2009","journal-title":"Annu. 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