{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T17:42:59Z","timestamp":1761154979107},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,12,28]],"date-time":"2006-12-28T00:00:00Z","timestamp":1167264000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Our previous studies have shown that murine dendritic cells (DCs) genetically modified to express interleukin\u20104 (IL\u20104) reduce the incidence and severity of murine collagen\u2010induced arthritis. The present studies were performed to assess the immunoregulatory mechanisms underlying this response, by assessing the effects of IL\u20104 DCs on cytokine production by subsets of T helper cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male DBA mice ages 6\u20138 weeks old were immunized with type II collagen. Splenic T cells obtained during the initiation phase and the end stage of arthritis were cultured with IL\u20104 DCs or untransduced DCs in the presence of collagen rechallenge. Interferon\u2010\u03b3 (IFN\u03b3) and IL\u201017 responses were measured. Antibodies to IL\u20104, IL\u201012, and IL\u201023, and recombinant IL\u20104, IL\u201012, and IL\u201023 were used to further study the regulation of T cell cytokine production by IL\u20104 DCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Splenic T cells obtained during the initiation phase of arthritis produced less IL\u201017 when cultured in the presence of IL\u20104 DCs, despite their production of increased quantities of other proinflammatory cytokines (IFN\u03b3 and tumor necrosis factor). T cell IL\u201017 production after collagen rechallenge was not inhibited by a lack of IL\u201023, since IL\u20104\u2013mediated suppression of IL\u201017 was not reconstituted by IL\u201023, an otherwise potent inducer of IL\u201017 production by T cells. Although IL\u20104 DCs can produce increased quantities of IL\u201012 and IFN\u03b3, suppression of IL\u201017 production by IL\u20104 DCs was independent of both. While IL\u201017 production by T cells obtained during the initiation phase of arthritis was regulated by IL\u20104 DCs, IL\u201017 production by T cells obtained during end\u2010stage arthritis was not altered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data suggest that IL\u20104 DCs exert a therapeutic effect on collagen\u2010induced arthritis by targeting IL\u201017. IL\u201017 suppression by IL\u20104 DCs is robust and is not reversed by IL\u201023. Timing might be important in IL\u201017\u2013targeted therapy, since IL\u201017 production by T cells obtained during end\u2010stage arthritis did not respond to suppression by IL\u20104 DCs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22311","type":"journal-article","created":{"date-parts":[[2006,12,28]],"date-time":"2006-12-28T23:51:08Z","timestamp":1167349868000},"page":"89-100","source":"Crossref","is-referenced-by-count":42,"title":["Interleukin\u201017 as a molecular target in immune\u2010mediated arthritis: Immunoregulatory properties of genetically modified murine dendritic cells that secrete interleukin\u20104"],"prefix":"10.1002","volume":"56","author":[{"given":"Sujata","family":"Sarkar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura 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