期刊
IMMUNITY
卷 55, 期 7, 页码 1173-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2022.05.010
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类别
资金
- NIH [R01AI034206, R01AI153174]
- NIH/NCI [P30 CA008748]
- AACR-Bristol-Myers Squibb Immuno-oncology Research Fellowship [19-4015-PRIT]
- Ludwig Center at MSKCC
- Cycle for Survival
- Marie-Josee and Henry R. Kravis Center for Molecular Oncology
The role of Foxp3 in peripheral pTreg cells and the mechanisms supporting their differentiation remain poorly understood. This study used genetic tracing to identify microbiota-induced pTreg cells and found that many of their distinguishing features were Foxp3 independent. While Foxp3 was critical for the suppression of certain diseases, pTreg cells could suppress colonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals preceding and promoting its expression confer distinct facets of pTreg functionality.
Regulatory T (Treg) cells expressing the transcription factor Foxp3 are an essential suppressive T cell lineage of dual origin: Foxp3 induction in thymocytes and mature CD4(+) T cells gives rise to thymic (tTreg) and peripheral (pTreg) Treg cells, respectively. While tTreg cells suppress autoimmunity, pTreg cells enforce tolerance to food and commensal microbiota. However, the role of Foxp3 in pTreg cells and the mechanisms supporting their differentiation remain poorly understood. Here, we used genetic tracing to identify microbiota-induced pTreg cells and found that many of their distinguishing features were Foxp3 independent. Lineage-committed, microbiota-dependent pTreg-like cells persisted in the colon in the absence of Foxp3. While Foxp3 was critical for the suppression of a Th17 cell program, colitis, and mastocytosis, pTreg cells suppressed colonic effector T cell expansion in a Foxp3-independent manner. Thus, Foxp3 and the tolerogenic signals that precede and promote its expression independently confer distinct facets of pTreg functionality.
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