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The collapse of immune tolerance, together with persistent synovial inflammation and pathogenic cytokine imbalances, jointly exacerbates joint injury. Here, we design a bioresponsive therapeutic platform composed of regulatory T cell (T\n                    <jats:sub>reg<\/jats:sub>\n                    )\u2010derived exosomes co\u2010loaded with growth arrest\u2010specific protein 6 (Gas6), engineered to preferentially home to inflamed joints via CCR2\u2010guided chemotactic targeting. The two components of the hybrid\u2014Gas6 and T\n                    <jats:sub>reg<\/jats:sub>\n                    exosomes\u2014exert both independent and synergistic immunomodulatory effects. By mitigating inflammation and reprogramming the tissue environment toward a tolerogenic state, the system bridges innate and adaptive immunity to restore overall immune function. In an MSU\u2010induced murine GA model, this therapy not only alleviates key clinical symptoms, but also promotes the expansion of regulatory T cells and suppresses T\n                    <jats:sub>H<\/jats:sub>\n                    17 responses, leading to restoration of a more tolerogenic immune balance. Together, our study presents a cell\u2010free, CCR2\u2010guided immunoengineering approach that achieves targeted delivery and coordinated immune reprogramming, offering a promising strategy for treating GA and other disorders associated with immune imbalance.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71311","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:35:26Z","timestamp":1780378526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CCR2\u2010Guided T\n                    <sub>reg<\/sub>\n                    Exosome\u2013Gas6 Hybrid Synergistically Reprograms Macrophage Inflammation and Immune Tolerance in Gouty Arthritis"],"prefix":"10.1002","volume":"15","author":[{"given":"Sang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Rheumatology Fujian Medical University Union Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Fujian Institute of Endocrinology Fujian Medical University Union Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3534-7480","authenticated-orcid":false,"given":"Jixin","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Fujian Medical University Union Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8430-7891","authenticated-orcid":false,"given":"Fangfang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Fujian Medical University Union Hospital  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202310492"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard\u20102022\u2010222764"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201062645\u20106"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01715-0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.05.021"},{"key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41584-024-01172-y","article-title":"The PU. 1\u2013IL\u20109 Axis in TH9 Cells Promotes RA","volume":"20","author":"Webster H.","year":"2024","journal-title":"Nature Reviews Rheumatology"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2017.04.008"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.06.005"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408363.2025.2539133"},{"key":"e_1_2_8_11_1","doi-asserted-by":"crossref","unstructured":"S. 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