{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T10:56:01Z","timestamp":1780656961251,"version":"3.54.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Despite intensive research on rheumatoid arthritis, the pathomechanism of the disease is still not fully understood and the treatment has not been completely resolved. Previously we demonstrated that the GTPase-activating protein, ARHGAP25 has a crucial role in the regulation of basic phagocyte functions. Here we investigate the role of ARHGAP25 in the complex inflammatory process of autoantibody-induced arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Wild-type and ARHGAP25 deficient (KO) mice on a C57BL\/6 background, as well as bone marrow chimeric mice, were treated i.p. with the K\/BxN arthritogenic or control serum, and the severity of inflammation and pain-related behavior was measured. Histology was prepared, leukocyte infiltration, cytokine production, myeloperoxidase activity, and superoxide production were determined, and comprehensive western blot analysis was conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the absence of ARHGAP25, the severity of inflammation, joint destruction, and mechanical hyperalgesia significantly decreased, similarly to phagocyte infiltration, IL-1\u03b2, and MIP-2 levels in the tibiotarsal joint, whereas superoxide production or myeloperoxidase activity was unchanged. We observed a significantly mitigated phenotype in KO bone marrow chimeras as well. In addition, fibroblast-like synoviocytes showed comparable expression of ARHGAP25 to neutrophils. Significantly reduced ERK1\/2, MAPK, and I-\u03baB protein signals were detected in the arthritic KO mouse ankles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that ARHGAP25 has a key role in the pathomechanism of autoantibody-induced arthritis in which it regulates inflammation <jats:italic>via<\/jats:italic> the I-\u03baB\/NF-\u03baB\/IL-1\u03b2 axis with the involvement of both immune cells and fibroblast-like synoviocytes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1182278","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T20:24:16Z","timestamp":1683750256000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Lacking ARHGAP25 mitigates the symptoms of autoantibody-induced arthritis in 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