{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:16:22Z","timestamp":1760058982218,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:00:00Z","timestamp":1747180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Basic Science Research Program of the Korean National Research Foundation","doi-asserted-by":"publisher","award":["NRF-2023R1A2C2002380"],"award-info":[{"award-number":["NRF-2023R1A2C2002380"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lysophosphatidylinositols are degradation products of phosphatidylinositols within cell membranes and digestive metabolites of a high-fat diet in the gut. G-protein-coupled receptor 55 (GPR55) is a receptor that senses lysophosphatidylinositol and acts as an immune mediator, being primarily upregulated during immune cell activation. This study aimed to investigate the role of GPR55, using its antagonist, CID16020046, in a collagen-induced rheumatoid arthritis mouse model. It was observed that DBA-1J mice develop joint lesions characteristic of rheumatoid arthritis following immunization with bovine type II collagen. The administration of CID16020046 (1 mg\/kg, intraperitoneally) alleviated rheumatoid arthritis symptoms and inflammatory responses. Histopathological analysis showed that CID16020046 reduced foot edema, proteoglycan loss, and bone erosion in the joints. CID16020046 also decreased rheumatoid-arthritis-induced serum IgG levels, as measured using enzyme-linked immunosorbent assays. The treatment reduced levels of pro-inflammatory cytokines (IL-1\u03b2 and IL-6), Th1 cytokine (IFN-\u03b3), and Th17 cytokine (IL-17A), along with matrix metalloproteinase-3 (MMP-3) and the receptor activator of nuclear factor-\u03baB ligand (RANKL) in the feet. A significant reduction in splenomegaly was also observed, along with significant reductions in CD4+ T helper 1 (Th1) and Th17 cells in the spleen. Additionally, CID16020046 suppressed the differentiation of na\u00efve T cells into CD4+IL-17+ Th17 cells. CID16020046 suppressed expression levels of inflammatory cytokine mRNAs in SW982 human synovial cells. In conclusion, blocking GPR55 alleviates collagen-induced rheumatoid arthritis symptoms by suppressing Th1 and Th17 cells in the spleen and pro-inflammatory cytokines in the joints, suggesting that GPR55 is a potential therapeutic target for autoimmune inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms26104680","type":"journal-article","created":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T10:27:41Z","timestamp":1747218461000},"page":"4680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPR55 Antagonist CID16020046 Suppresses Collagen-Induced Rheumatoid Arthritis by Suppressing Th1\/Th17 Cells in Mice"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-7881","authenticated-orcid":false,"given":"Jung-Eun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-8946","authenticated-orcid":false,"given":"Dong-Soon","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea"},{"name":"Department of Basic Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02446, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/j.tips.2018.02.011","article-title":"Lysophosphatidylinositols, from Cell Membrane Constituents to GPR55 Ligands","volume":"39","author":"Alhouayek","year":"2018","journal-title":"Trends Pharmacol. 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