Immunoregulatory actions of Treg PPAR gamma in the gut mucosa

Bassaganya-Riera, J and R. Hontecillas (2007) Immunoregulatory actions of Treg PPAR gamma in the gut mucosa. AAI Annual Meeting, Boston, MA. (Abstract #59).

Peroxisome proliferator-activated receptor (PPAR) γ activation has been implicated in the prevention of immunoinflammatory disorders, however the mechanisms of immune modulation by endogenous PPAR γ agonists remain unclear. We have used PPAR γ- deficient CD4+ T cells obtained from tissue-specific PPAR γ null mice (i.e., PPAR γ fl/fl; MMTV-Cre+) to investigate the role of endogenous PPAR γ on regulatory CD4+ T cell (Treg) function. Overall, we show that the transfer of purified PPAR γ null CD4+ T cells into SCID recipients results in enteric disease. To test the assertion that the deficiency of PPAR γ in Treg impairs their ability to prevent effector T cell-induced colitis, we performed co-transfer studies using PPAR γ null and PPAR γ-expressing CD4+ T cells. These studies demonstrate that PPAR γ-expressing, but not PPAR γ null Treg, prevent colitis induced by transfer of naïve CD4+ T cells into SCID recipients. In line with these findings, the production of IFN-γ by spleen and mesenteric lymph node-derived CD4+ T cells was down-regulated following transfer of PPAR γ-expressing, but not PPAR γ null, Treg. Furthermore, the loss of PPAR γ limited the expansion of Foxp3+ cells systemically and their accumulation in the colonic mucosa. In conclusion, our data suggest that endogenous PPAR γ activation represents a Treg intrinsic mechanism of down regulation of effector CD4+ T cell function and prevention of intestinal inflammation.