Tregs are dysfunctional in vivo in a spontaneous murine model of Crohn's disease

• DOI: 10.1038/mi.2012.67
• Publication Date: 2012-07-11T12:31:14Z
• Authors: D Ishikawa; A Okazawa; D Corridoni; L G Jia; X M Wang; M Guanzon; W Xin; K O Arseneau; T T Pizarro; F Cominelli
• Keywords: Ileitis; Adoptive Cell Transfer; Mesenteric lymph nodes

Although regulatory T cells (Tregs) have been implicated in inflammatory bowel disease, Tregs from Crohn's disease (CD) patients are increased number and function normally vitro. To clarify this disparity, we studied Treg vivo using a spontaneous model of CD-like ileitis. We first administered anti-CD25-depleting antibodies to SAMP1/YitFc (SAMP) mice assess ileitis; mesenteric lymph node were then transferred into SCID (severe combined immunodeficient) recipients induce colitis. CD25 depletion the severity both ileitis adoptively Interestingly, second transfer CD4(+)CD25(+) untreated AKR control was able ameliorate induced colitis, whereas SAMP not, suggesting functional abnormality Tregs. Anti-CD25 treatment also proliferation CD25(-)Foxp3(+) Tregs, which had proinflammatory intestinal helper type 1/ 2 (Th1/Th2) effector phenotype. These studies demonstrate dysfunction