S-1: Complexity of cytokines in Treg function and stability

Autoimmunity is a direct consequence of a lack of immune homeostasis and unregulated destruction of self-tissues. The lack of regulation has been attributed to the reduced efficacy of a highly specialized regulatory T cell (Treg). Accumulating evidence suggests that defective regulation is due, at least in part, to the instability and loss of Tregs in the inflamed tissues. Treg instability and loss results from reduced IL-2 sensitivity and IL-2 signaling via STAT5 as instability is reversed, and immune regulation restored, with IL-2 therapy. In addition, recent data suggest that the inflammatory milieu can alter cytokine activities including TGFb. This presentation will focus on several aspects of Treg, IL-2 and TGFb biology including their function and stability in mouse and human autoimmune settings. This work is supported by NIH, JDRF and Pfizer Corp.