Genetic tracing reveals transcription factor Foxp3-dependent and Foxp3-independent functionality of peripherally induced Treg cells

Joris van der Veeken, Clarissa Campbell, Yuri Pritykin, Michail Schizas, Jacob Verter, Wei Hu, Zhong Min Wang, Fanny Matheis, Daniel Mucida, Louis Marie Charbonnier, Talal A. Chatila, Alexander Y. Rudensky

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1173-1184.e7
JournalImmunity
Volume55
Issue number7
DOIs
StatePublished - Jul 12 2022

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Keywords

  • Foxp3
  • lineage tracing
  • microbiota
  • peripherally induced Treg
  • Treg

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