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We examined the Ras\u2010inhibitory effect on functional determinants of Treg <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Ras was inhibited in Jurkat T cells by transfection with a dominant\u2010negative form of Ras, or by shRNA for N\u2010Ras, K\u2010Ras, and H\u2010Ras, or by farnesylthiosalycylic acid, a small\u2010molecule inhibitor. Except for H\u2010Ras transduction with shRNA, each inhibitory mode increased expression of Foxp3 and nuclear factor of activated T cell proteins, and surface expression of CD25. Ras inhibition in PBMC and spleen\u2010derived lymphocytes reproduced these findings. The heightened Foxp3 expression reflected both increased basal cellular protein and peripheral conversion of non\u2010Treg to Treg. Ras inhibition enhanced Treg\u2010induced suppression; thus, when adoptively transferred to mice, Ras\u2010inhibited Treg reduced the incidence of diabetes. Inhibition of Foxp3 by respective siRNA reversed the enhancement. Thus, inhibition of the N\u2010 or K\u2010Ras isoform triggers an anti\u2010inflammatory effect by up\u2010regulating, <jats:italic>via<\/jats:italic> Foxp3 elevation, the numbers and functional suppressive properties of Treg.<\/jats:p>","DOI":"10.1002\/eji.200838292","type":"journal-article","created":{"date-parts":[[2008,5,6]],"date-time":"2008-05-06T17:56:14Z","timestamp":1210096574000},"page":"1493-1502","source":"Crossref","is-referenced-by-count":30,"title":["N\u2010Ras or K\u2010Ras inhibition increases the number and enhances the function of Foxp3 regulatory T cells"],"prefix":"10.1002","volume":"38","author":[{"given":"Adi","family":"Mor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gad","family":"Keren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoel","family":"Kloog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5,20]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1172\/JCI23215","article-title":"IL\u201010\u2010producing and naturally occurring CD4+ Tregs: limiting collateral damage.","volume":"114","author":"O'Garra A.","year":"2004","journal-title":"J. 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