{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:21:07Z","timestamp":1790655667111,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["24K11597"],"award-info":[{"award-number":["24K11597"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a multistep pathogenesis, from the preclinical phase of autoantibody emergence to the clinical onset of synovitis and joint destruction. Cytokines play central roles throughout this progression by orchestrating immune cell activation, tissue inflammation, and bone erosion. In the preclinical phase, several cytokines, including IL-12, IL-6, IL-21 and TGF-\u03b2, promote Tfh and Tph cell differentiation, helping autoreactive B cells to produce ACPA. During the clinical phase, TNF-\u03b1, IL-6, and IL-1\u03b2 drive synovitis by activating macrophages and fibroblast-like synoviocytes, while also promoting RANKL (Receptor Activator of Nuclear factor \u03baB Ligand) expression and osteoclast differentiation. This review highlights the pathogenic role of cytokines in RA and discusses their relevance as biomarkers and therapeutic targets. A better understanding of cytokine networks may offer new opportunities for early intervention and disease prevention in RA.<\/jats:p>","DOI":"10.3390\/jcm14186409","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T14:23:50Z","timestamp":1757600630000},"page":"6409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Pathogenic Role of Cytokines in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"14","author":[{"given":"Sho","family":"Fujimoto","sequence":"first","affiliation":[{"name":"Department of Medical Education, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0914-9066","authenticated-orcid":false,"given":"Hiroaki","family":"Niiro","sequence":"additional","affiliation":[{"name":"Department of Medical Education, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1002\/art.20018","article-title":"Specific Autoantibodies Precede the Symptoms of Rheumatoid Arthritis: A Study of Serial Measurements in Blood Donors","volume":"50","author":"Nielen","year":"2004","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.1076","article-title":"Five Amino Acids in Three HLA Proteins Explain Most of the Association between MHC and Seropositive Rheumatoid Arthritis","volume":"44","author":"Raychaudhuri","year":"2012","journal-title":"Nat. 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