Document Type

Article

Publication Date

2021

DOI

10.1038/s41385-020-00349-4

Publication Title

Mucosal Immunology

Volume

14

Issue

2

Pages

443-454

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− T (Tn) cells to the Treg lineage. Overall, data presented here suggest that Tan induction helps the Treg repertoire to become optimally balanced to provide tolerance toward ubiquitous and microbiome-derived epitopes, improving host ability to avert systemic autoimmunity and intestinal inflammation.

Rights

This article is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Data Availability

Article states: "All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper can be requested from the authors."

"The online version of this article (https://doi.org/10.1038/s41385-020-00349-4) contains supplementary material, which is available to authorized users."

Corresponding author: Leszek Ignatowicz

Original Publication Citation

Kuczma, M.P., Szurek, E.A., Cebula, A., Ngo, V.L., Pietrzak, M., Kraj, P., Denning, T.L., & Ignatowicz, L. (2021) Self and microbiota-derived epitopes induce CD4⁺ T cell anergy and conversion into CD4⁺Foxp3⁺ regulatory cells. Mucosal Immunology 14(2), 443-454. https://doi.org/10.1038/s41385-020-00349-4

ORCID

0000-0003-2122-5105 (Kraj)

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