A central role for Atg5 in microbiota-dependent Foxp3\(^{+}\) ROR\(\gamma\)t\(^{+}\) 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, ROR\(\gamma\)t-expressing Treg cells have been identified as key regulators of gut homeostasis, preventing intestinal immunopathology. To study the role of autophagy in ROR\(\gamma\)t\(^{+}\) 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 ROR\(\gamma\)t\(^{+}\) Foxp3\(^{+}\) subpopulation of Treg cells was most severely affected. Our data indicated that autophagy is essential to maintain the intestinal ROR\(\gamma\)t\(^{+}\) Foxp3\(^{+}\) Treg population, thereby protecting the mice from gut inflammatory disorders.
Author: | Carlos Plaza SirventORCiDGND, Bei ZhaoGND, Alisha W. BronietzkiGND, Marina C. PilsGND, Neda TafrishiGND, Marc SchusterGND, Till StrowigGND, Ingo SchmitzORCiDGND |
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URN: | urn:nbn:de:hbz:294-88056 |
DOI: | https://doi.org/10.3389/fimmu.2021.705436 |
Parent Title (English): | Frontiers in immunology |
Publisher: | Frontiers |
Place of publication: | Lausanne |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2022/03/31 |
Date of first Publication: | 2021/08/26 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds Atg5; ROR\(\gamma\)t\(^{+}\) Foxp3\(^{+}\) Treg cells; autophagy; inflammation; intestinal homeostasis |
Volume: | 12 |
Issue: | Article 705436 |
First Page: | 705436-1 |
Last Page: | 705436-14 |
Note: | Article Processing Charge funded by the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Lehrstuhl für Molekulare Immunologie |
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
open_access (DINI-Set): | open_access |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |