The IL–10/STAT3 axis: Contributions to immune tolerance by thymus and peripherally derived regulatory T‐cells

The signal transducer and activator of transcription (STAT) proteins are important mediators for the integration of extrinsic signals provided by cytokines and hormones and thereby adapt cellular processes to their surroundings. In the past decade, the involvement of STAT3 in the regulation of T‐cell responses has become a topic of increasing interest. STAT3 is activated in response to multiple cytokines, many of which have been shown to influence T‐cell responses. Interestingly, many of these factors have been described with apparent opposing roles, such as the highly pro–inflammatory potency of IL–6 and the anti–inflammatory properties of IL–10, thus raising the possibility that STAT3 signaling may fulfill diverse roles in CD4+ T‐cells. Here, we review the contribution of STAT3 to the induction and function of both peripherally induced as well as thymus‐derived regulatory T‐cells. Indeed, experimental approaches as well as studies of human patients suffering from e.g. Job's (hyper IgE) syndrome or inflammatory bowel disease (IBD) have now established a clear–cut role for the IL–10/STAT3 axis in immune tolerance; further understanding of these processes could lead to novel therapeutic approaches for autoimmune diseases. The IL–10/STAT3 axis intergrates signals provided by extrinsic cues to shape CD4+ T‐cell responses. Important findings from knockout and overexpression studies indicate that IL10/STAT3 signaling limits T‐helper cell effector functions and promotes tolerance‐associated cellular programs. This tolerogenic role of the IL–10/STAT3 axis is presented and critically discussed in the present review.