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.
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
Kuczma, Michal P.; Szurek, Edyta A.; Cebula, Anna; Ngo, Vu L.; Pietrzak, Maciej; Kraj, Piotr; Denning, Timothy L.; and Ignatowicz, Leszek, "Self and Microbiota-Derived Epitopes Induce CD4⁺ T Cell Anergy and Conversion into CD4⁺Foxp3⁺ Regulatory Cells" (2021). Biological Sciences Faculty Publications. 472.