{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:43:19Z","timestamp":1787236999602,"version":"build-2736575974"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Adjuvant-induced arthritis (AIA) serves as a classic model for rheumatoid arthritis (RA), typified by inflammatory cell infiltration and joint damage. This study explores the therapeutic efficacy of HU-308, a CB2 receptor-specific agonist, on inflammation and immune balance in AIA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      AIA was induced in mice by CFA injection. AIA mice were treated with HU-308 or vehicle, and effects on paw swelling, spleen index, histopathology, and immune cell profiles were evaluated. Flow cytometry,\n                      <jats:italic>in vitro<\/jats:italic>\n                      differentiation assays, and Western blot analysis were performed to examine Th17 and Treg cells, as well as signaling pathways involved in their differentiation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HU-308 reduced paw swelling, lowered spleen index, and preserved joint integrity in AIA mice, mitigating inflammatory cell infiltration and bone erosion. Flow cytometry revealed that HU-308 restored the Th17\/Treg imbalance in AIA, decreasing Th17 cell frequency and enhancing Treg cell infiltration.\n                      <jats:italic>In vitro<\/jats:italic>\n                      assays confirmed HU-308s role in promoting Treg differentiation and inhibiting Th17 polarization. Western blot analysis indicated that HU-308 modulated immune balance through the JAK\/STAT5 and TGF-\u03b2\/SMAD signaling pathways, increasing Foxp3 and TGF-\u03b2 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HU-308 demonstrates significant anti-inflammatory effects in AIA by restoring Th17\/Treg balance and reducing joint damage. The findings indicate that HU-308 holds potential as an immunomodulatory agent for RA, providing valuable insights into CB2-mediated therapeutic strategies for autoimmune diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1532518","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T01:40:39Z","timestamp":1738287639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Cannabinoid receptor 2 selective agonist ameliorates adjuvant-induced arthritis by modulating the balance between Treg and Th17 cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Na","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Ming","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.intimp.2014.01.005","article-title":"Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide treatment","volume":"19","author":"Ahmad","year":"2014","journal-title":"Int. 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