{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T23:25:27Z","timestamp":1769124327629,"version":"3.49.0"},"reference-count":55,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2005,8,1]],"date-time":"2005-08-01T00:00:00Z","timestamp":1122854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2005,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>In rheumatoid arthritis (RA), a widespread autoimmune\/inflammatory joint disease, early activation of effector CD4+ T lymphocytes, and cytokine production is followed by recruitment of other inflammatory cells, production of a range of inflammation mediators, tissue damage, and disease. GITR (glucocorticoid\u2010induced TNFR family\u2010related gene), a costimulatory molecule for T lymphocytes, increases CD4+CD25\u2212 effector T cell activation while inhibiting suppressor activity of CD4+CD25+ T regulatory (Treg) cells. We analyzed the role of GITR in type II collagen (CII) \u2010induced arthritis (CIA) using GITR\u2212 \/\u2212 and GITR+ \/ + mice. Results indicate significantly less CIA induction in GITR\u2212\/\u2212 mice than in GITR+\/+ mice, with marked differences in erythema, edema, neutrophil infiltration, joint injury, and bone erosion. Production of IFN\u03b3, IL\u20106, TNF\u03b1, MIP\u20101\u03b1, and MIP\u20102, inducible NOS (iNOS), COX\u20102, and nitrotyrosine poly\u2010ADP\u2010ribose (PAR) were also less in CII\u2010treated GITR\u2212\/\u2212 mice. Although CD4+CD25+ Treg cells from GITR+\/+ and GITR\u2212\/\u2212 CII\u2010challenged mice exerted similar suppressor activity in vitro, GITR triggering abrogated GITR+\/+ Treg suppressor activity and costimulated CD4+CD25\u2212 GITR+\/+ effector cells. Furthermore, Treg cells from GITR\u2212\/\u2212 protected more than Treg cells from GITR+\/+ mice against CIA when cotransferred with Treg\u2010depleted splenocytes from arthritic GITR+\/+ animals into severe combined immunodeficient (SCID) mice. In conclusion, GITR plays a critical role in the immunological response against CII and in the development of CIA. Cuzzocrea, S., Ayroldi, E., Di Paola, R., Agostini, M., Mazzon, E., Bruscoli, S., Genovese, T., Ronchetti, S., Caputi, A. P., Riccardi, C. Role of glucocorticoid\u2010induced TNF receptor family gene (GITR) in collagen\u2010induced arthritis. 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