{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:50:40Z","timestamp":1790567440918,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["19K08880"],"award-info":[{"award-number":["19K08880"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,8]]},"abstract":"<jats:p>\n                    Immunoproteasomes regulate the degradation of ubiquitin-coupled proteins and generate peptides that are preferentially presented by MHC class I. Mutations in immunoproteasome subunits lead to immunoproteasome dysfunction, which causes proteasome-associated autoinflammatory syndromes (PRAAS) characterized by nodular erythema and partial lipodystrophy. It remains unclear, however, how immunoproteasome dysfunction leads to inflammatory symptoms. Here, we established mice harboring a mutation in\n                    <jats:italic>Psmb8<\/jats:italic>\n                    (Psmb8-KI mice) and addressed this question. Psmb8-KI mice showed higher susceptibility to imiquimod-induced skin inflammation (IMS). Blockade of IL-6 or TNF-\u03b1 partially suppressed IMS in both control and Psmb8-KI mice, but there was still more residual inflammation in the Psmb8-KI mice than in the control mice. DNA microarray analysis showed that treatment of J774 cells with proteasome inhibitors increased the expression of the\n                    <jats:italic>Cxcl9<\/jats:italic>\n                    and\n                    <jats:italic>Cxcl10<\/jats:italic>\n                    genes. Deficiency in\n                    <jats:italic>Cxcr3<\/jats:italic>\n                    , the gene encoding the receptor of CXCL9 and CXCL10, in control mice did not change IMS susceptibility, while deficiency in Cxcr3 in Psmb8-KI mice ameliorated IMS. Taken together, these findings demonstrate that this mutation in\n                    <jats:italic>Psmb8<\/jats:italic>\n                    leads to hyperactivation of the CXCR3 pathway, which is responsible for the increased susceptibility of Psmb8-KI mice to IMS. These data suggest the CXCR3\/CXCL10 axis as a new molecular target for treating PRAAS.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.152681","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T08:36:17Z","timestamp":1649406977000},"source":"Crossref","is-referenced-by-count":13,"title":["Blockade of the CXCR3\/CXCL10 axis ameliorates inflammation caused by immunoproteasome dysfunction"],"prefix":"10.1172","volume":"7","author":[{"given":"Yuki","family":"Sasaki","sequence":"first","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Arimochi","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiro","family":"Otsuka","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine,"},{"name":"Department of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Tsukumo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine,"},{"name":"Department of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Yasutomo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Parasitology, Graduate School of Medicine,"},{"name":"Department of Interdisciplinary Research for Medicine and Photonics, Institute of Post-LED Photonics, Tokushima, and"},{"name":"The Research Cluster Program on Immunological Diseases, Tokushima University, Tokushima, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2687"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2012.11.004"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax3769"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0186-z"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1126\/science.8066462"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2013.09.010"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2630"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90043-4"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/science.8066463"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6665"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3480"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58414"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.10.031"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1106015108"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1172\/JCI81260"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98814"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/srep26791"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.12695"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-090413-025334"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00927"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.10.010"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2015.00609","article-title":"The role of chemokines in shaping the balance between CD4(+) T cell subsets and its therapeutic implications in autoimmune and cancer diseases","volume":"6","author":"Karin","year":"2015","journal-title":"Front Immunol"},{"key":"B23","article-title":"Overview of the mechanisms that may contribute to the non-redundant activities of interferon-inducible CXC chemokine receptor 3 ligands","volume":"8","author":"Metzemaekers","year":"2017","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.02.012"},{"issue":"4","key":"B25","doi-asserted-by":"crossref","DOI":"10.1210\/clinem\/dgz289","article-title":"Th1 chemokines in autoimmune endocrine disorders","volume":"105","author":"Fallahi","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/1546-0096-11-38"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.01.015"},{"key":"B28","article-title":"Hematopoietic stem 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