{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:43:39Z","timestamp":1760204619648},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,28]],"date-time":"2013-01-28T00:00:00Z","timestamp":1359331200000},"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":[[2013,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Despite the importance of Treg cells in the maintenance of immunologic tolerance, the mechanisms that control their generation and activity are unknown. Since the cell cycle inhibitor p27<jats:sup>Kip1<\/jats:sup> (p27) was involved in T cell anergy, we undertook this study to explore its role in both Treg cell processes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The development of type II collagen\u2013induced arthritis (CIA) and lupus\u2010like abnormalities was compared between transgenic mice overexpressing human Bcl\u20102 in T cells (BCL2\u2010TgT mice) and nontransgenic mice that were deficient or not deficient in p27. The contribution of Treg cells to disease evolution was also explored. Finally, the in vitro activity of Treg cells and their differentiation from naive CD4+ cells was compared between these strains of mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BCL2\u2010TgT mice were protected against CIA by a Treg cell\u2013dependent mechanism. In association with this protection, the overexpression of Bcl\u20102 in T cells enhanced the differentiation and activity of Treg cells. Both Bcl\u20102 effects were independent of its antiapoptotic activity but dependent on its capacity to induce the expression of p27 that augmented the strength of transforming growth factor \u03b2 (TGF\u03b2) signaling in T cells. Accordingly, down\u2010modulation of p27 expression in BCL2\u2010TgT mice promoted CIA. In addition, p27 deficiency in aged C57BL\/6 mice reduced the number and activity of Treg cells and induced the development of mild lupus\u2010like abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results point to p27 as a critical regulator of Treg cell differentiation and function through the positive modulation of TGF\u03b2 signaling strength in T cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37778","type":"journal-article","created":{"date-parts":[[2012,11,2]],"date-time":"2012-11-02T17:37:19Z","timestamp":1351877839000},"page":"343-354","source":"Crossref","is-referenced-by-count":12,"title":["p27<sup>Kip1<\/sup> inhibits systemic autoimmunity through the control of Treg cell activity and differentiation"],"prefix":"10.1002","volume":"65","author":[{"given":"Marcos","family":"Iglesias","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Postigo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In\u00e9s","family":"Santiuste","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jovanna","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Buelta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Tamayo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Merino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ram\u00f3n","family":"Merino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,1,28]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic 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