{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:24:29Z","timestamp":1785176669207,"version":"3.55.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,12,1]],"date-time":"2013-12-01T00:00:00Z","timestamp":1385856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Th17 cells play a critical role in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms by which these cells regulate the development of RA are not fully understood. We have recently shown that \u03b12\u03b21 integrin, the receptor of type I collagen, is the major collagen-binding integrin expressed by human Th17 cells. In this study, we examined the role of \u03b12\u03b21 integrin in Th17-mediated destructive arthritis in the murine model of collagen-induced arthritis (CIA). We found that \u03b12\u03b21 integrin is expressed on synovial Th17 cells from CIA mice and its neutralization with a specific mAb significantly reduced inflammation and cartilage degradation, and protected the mice from bone erosion. Blockade of \u03b12\u03b21 integrin led to a decrease in the number of Th17 cells in the joints and to a reduction of IL-17 levels in CIA mice. This was associated with an inhibition of receptor activator of NF-\u03baB ligand levels and osteoclast numbers, and reduction of bone loss. We further show that \u03b12\u03b21 integrin is expressed on synovial Th17 cells from RA patients, and that its ligation with collagen costimulated the production of IL-17 by polarized human Th17 cells by enhancing the expression of retinoic acid receptor\u2013related orphan receptor C through ERK and PI3K\/AKT. Our findings provide the first evidence, to our knowledge, that \u03b12\u03b21 integrin is an important pathway in Th17 cell activation in the pathogenesis of CIA, suggesting that its blockade can be beneficial for the treatment of RA and other Th17-associated autoimmune diseases.<\/jats:p>","DOI":"10.4049\/jimmunol.1301940","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T03:43:24Z","timestamp":1384573404000},"page":"5941-5950","source":"Crossref","is-referenced-by-count":25,"title":["\u03b12\u03b21 Integrin Regulates Th17 Cell Activity and Its Neutralization Decreases the Severity of Collagen-Induced Arthritis"],"prefix":"10.1093","volume":"191","author":[{"given":"Mohammed-Amine","family":"El Azreq","sequence":"first","affiliation":[{"name":"Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec, Ville de Qu\u00e9bec , Qu\u00e9bec G1V 4G2,","place":["Canada"]},{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine de l\u2019Universit\u00e9 Laval, Ville de Qu\u00e9bec , Qu\u00e9bec G1V 0A6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Boisvert","sequence":"additional","affiliation":[{"name":"Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de Recherche du Centre Hospitalier Universitaire de Qu\u00e9bec, Ville de Qu\u00e9bec , Qu\u00e9bec G1V 4G2,","place":["Canada"]},{"name":"D\u00e9partement de Microbiologie-Infectiologie et d\u2019Immunologie, Facult\u00e9 de M\u00e9decine de l\u2019Universit\u00e9 Laval, Ville de Qu\u00e9bec , Qu\u00e9bec G1V 0A6,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Cesaro","sequence":"additional","affiliation":[{"name":"Axe de Recherche sur les Maladies Infectieuses et Immunitaires, Centre de 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