A Central Role for Atg5 in Microbiota-Dependent Foxp3 + RORγt + Treg Cell Preservation to Maintain Intestinal Immune Homeostasis.

Autophagy is an evolutionary conserved catabolic pathway that ensures the degradation of intracellular components. The autophagic pathway is regulated by autophagy-related (Atg) proteins that govern formation of double-membraned vesicles called autophagosomes. Autophagy deficiency in regulatory T (Treg) cells leads to increased apoptosis of these cells and to the development of autoimmune disorders, predominantly characterized by intestinal inflammation. Recently, RORγt-expressing Treg cells have been identified as key regulators of gut homeostasis, preventing intestinal immunopathology. To study the role of autophagy in RORγt ⁺ Foxp3 ⁺ Treg cells, we generated mice lacking the essential component of the core autophagy machinery Atg5 in Foxp3 ⁺ cells. Atg5 deficiency in Treg cells led to a predominant intestinal inflammation. While Atg5-deficient Treg cells were reduced in peripheral lymphoid organs, the intestinal RORγt ⁺ Foxp3 ⁺ subpopulation of Treg cells was most severely affected. Our data indicated that autophagy is essential to maintain the intestinal RORγt ⁺ Foxp3 ⁺ Treg population, thereby protecting the mice from gut inflammatory disorders.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Plaza-Sirvent, Zhao, Bronietzki, Pils, Tafrishi, Schuster, Strowig and Schmitz.)