Role of STAT3 in regulatory T lymphocyte plasticity during acute graft-vs.-host-disease

Regulatory T (Treg) lymphocytes are important mediators of the allogeneic immune response, although the mechanisms by which they are controlled are not fully understood. Studies conducted in mice, including a recent article in Immunity by Laurence et al., have shown that STAT3 is an important factor involved in the instability of natural Treg (nTreg) lymphocytes and the generation of induced Treg (iTreg) lymphocytes. The authors used T lymphocytes obtained from Foxp3-GFP reporter mice, which allowed them to track the in vivo fate of the nTreg and iTreg lymphocyte populations in the inflammatory milieu of acute GvHD. They showed that nTreg lymphocytes lose the expression of FoxP3 within this inflammatory environment and that the loss of FoxP3 is, in part, STAT3-dependent. Ultimately, the absence of STAT3 permitted the conversion of transferred naive CD4(+) T lymphocytes to iTreg lymphocytes, which correlated with a strikingly improved survival rate during GvHD. We herein discuss how the article by Laurence et al. offers a novel mechanism to explain how the inflammatory environment may alter the stability or phenotype of Treg lymphocytes.