Self and microbiota-derived epitopes induce CD4⁺ T cell anergy and conversion into CD4⁺Foxp3⁺ regulatory cells.

ABSTRACT: The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4⁺CD44⁺Foxp3^-CD73⁺FR4⁺ anergic (Tan) cells expands the CD4⁺Foxp3⁺ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila commensal bacteria can induce anergy and drive conversion of naive CD4⁺CD44^-Foxp3^-

SUBMITTER: Kuczma MP 

PROVIDER: S-EPMC7946630 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature