Signals that induce IL-10 production by peripheral regulatory T cells

Abstract Inflammatory bowel disease (IBD) is an immune-mediated disease of the intestinal tract caused by chronic inflammation that can be relapsing and remitting. This inflammation leads to flares that often require patients to be treated with life-long biologic therapy. Interleukin 10 (IL-10) is an immunosuppressive cytokine produced by effector T cells, especially regulatory T cells (Tregs), to limit inflammatory responses to both foreign and self-antigens. Although IL-10-producing peripheral Tregs (IL-10+ pTregs) are thought to play a mitigating role in murine models of colitis, signals that control transcriptional regulation of the Il10 locus are not well understood. Here, we have examined cytokine and non-cytokine signals that enhance the induction of IL-10+ pTregs in vitro and in vivo. We find that in vitro a mix of inflammatory cytokines acting in concert with IL-2 and on-going TGFβ signaling induce the production of Foxp3+IL-10+ pTregs from Foxp3+IL-10- precursors. Ongoing studies are directed at extending these findings to the in vivo induction of IL-10-producing pTreg cells, and examining the ability of these cells to curb intestinal inflammation driven by aberrant effector T cell responses against the intestinal microbiota. Ultimately, we hope that by identifying signals to amplify our target population, we can perform genomic analyses to better decipher what modulates the transcriptional landscape of the Il10 locus, and identify novel immune therapies for patients with IBD.