SUMMARY
Regulatory T (Treg) cells represent a specialized CD4+ T cell lineage with essential anti-inflammatory functions. Recent studies of the adaptations of Treg cells to non-lymphoid tissues which enable their specialized immunosuppressive and tissue supportive functions raise questions about the underlying mechanisms of these adaptations and whether they represent stable differentiation or reversible activation states. Using novel genetic tools, we characterized the transcriptional programs of distinct colonic effector Treg cell types. We found that attenuated T cell receptor (TCR) signaling and acquisition of substantial TCR independent functionality appears to facilitate the terminal differentiation of a population of colonic effector Treg cells distinguished by stable expression of immunomodulatory cytokine interleukin-10 (IL-10). Functional studies revealed that this subset of effector Treg cells, but not their expression of IL-10, was indispensable for preventing colitis. These findings suggest core features of terminal differentiation of effector Treg cells in non-lymphoid tissues and their function therein.
Competing Interest Statement
A.Y.R. is an SAB member and has equity in Sonoma Biotherapeutics, RAPT Therapeutics, Surface Oncology, and Vedanta Biosciences, and is an SAB member of BioInvent and a co-inventor or has IP licensed to Takeda that is unrelated to the content of the present study. The remaining authors declare no competing interests.
Footnotes
↵5 Senior author
Figure S2 becomes Figure 4; new Figure S2 added. Text updated accordingly. Some updates to methods.
