{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T17:04:04Z","timestamp":1788627844157,"version":"build-2803163510"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"13","funder":[{"DOI":"10.13039\/100007428","name":"Naito Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H01026"],"award-info":[{"award-number":["19H01026"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JSPS KAKENHI JP22H04925 PAGS"],"award-info":[{"award-number":["JSPS KAKENHI JP22H04925 PAGS"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kobayashi Foundation"},{"name":"Institute for Life and Medical Sciences, Kyoto University"},{"name":"NOVARTIS Foundation for Promotion of Science"},{"name":"Katou Memorial Trust for Nambyo Research"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:p>\n                    Autoimmune T cells orchestrate joint inflammation and pain in concert with synovial macrophages; however, the mechanisms governing the development and functional diversification of these macrophages remain unclear. Using a model of T helper 17 cell (T\n                    <jats:sub>H<\/jats:sub>\n                    17 cell)\u2013mediated autoimmune arthritis, we show that joint-infiltrating Ly6C\n                    <jats:sup>hi<\/jats:sup>\n                    monocytes in response to autoimmune T\n                    <jats:sub>H<\/jats:sub>\n                    17 cells, rather than resident synovial macrophages, are the primary mediators of disease pathogenesis. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical component of the pathogenic circuit driven by arthritogenic T\n                    <jats:sub>H<\/jats:sub>\n                    17 cells, does not contribute to monocyte recruitment to the synovium but facilitates their subsequent differentiation into functionally distinct synovial macrophage subsets, thereby amplifying joint inflammation. Single-cell RNA sequencing identified two GM-CSF\u2013dependent subpopulations of pathogenic synovial macrophages\u2014Arginase-1\n                    <jats:sup>+<\/jats:sup>\n                    and epithelial cell adhesion molecule (EpCAM)\n                    <jats:sup>+<\/jats:sup>\n                    clusters\u2014both expressing proinflammatory cytokines and matrix metalloproteinases. Notably, EpCAM\n                    <jats:sup>+<\/jats:sup>\n                    macrophages uniquely express\n                    <jats:italic toggle=\"yes\">Ccl17<\/jats:italic>\n                    , a pronociceptive mediator implicated in arthritic pain. Collectively, these findings delineate a GM-CSF\u2013driven program of macrophage diversification that underpins both joint inflammation and pain, implicating this axis in the chronic activation of inflammatory and nociceptive pathways in autoimmune arthritis.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aec0986","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:00:16Z","timestamp":1774461616000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Pathogenic GM-CSF drives functional diversification of inflammatory macrophages in autoimmune arthritis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6871-5182","authenticated-orcid":true,"given":"Hiroki","family":"Mukoyama","sequence":"first","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."},{"name":"Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2491-9524","authenticated-orcid":true,"given":"Yusuke","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."},{"name":"Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7946-6352","authenticated-orcid":true,"given":"Daiya","family":"Ohara","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."},{"name":"The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8098-9966","authenticated-orcid":true,"given":"Yoonha","family":"Lee","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-9966","authenticated-orcid":true,"given":"Hitomi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9571-4895","authenticated-orcid":true,"given":"Hiroki","family":"Kato","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Immunology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2564-0149","authenticated-orcid":true,"given":"Gen","family":"Kondoh","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Morinobu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4737-0661","authenticated-orcid":true,"given":"Keiji","family":"Hirota","sequence":"additional","affiliation":[{"name":"Laboratory of Integrative Biological Science, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan."},{"name":"Institute of Cardiovascular Immunology, Medical Faculty, University Hospital Bonn, University of Bonn, Bonn, Germany."},{"name":"Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan."},{"name":"Cell Therapy Center, China Medical University Hospital, Taichung, Taiwan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00790-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.022"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm5658"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501372112"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI87828"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190945"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.08.010"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar318"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2014-205234"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-016-1185-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.40323"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-019-1879-x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30229-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302040"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01117-7"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200421795"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02119"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092301"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062259"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-024-01218-x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.04.009"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1471-1"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9644"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.08.026"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242847"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2012.89"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2370"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20230923"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.09.003"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-04-215020"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.08.011"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.25002"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01819-6"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.102397"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI96832"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-0172(00)80012-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1053\/joca.1998.0116"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/38.1.34"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-016-9113-1"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.99249"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.2.890"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.09.032"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-213250"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20220595"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2268-19.2020"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-225434"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aec0986","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T18:00:40Z","timestamp":1774461640000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aec0986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,27]]},"references-count":48,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2026,3,27]]}},"alternative-id":["10.1126\/sciadv.aec0986"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aec0986","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,27]]},"assertion":[{"value":"2025-09-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaec0986"}}