AUTHOR=Welsh Robin A. , Song Nianbin , Park Chan-Su , Peske J. David , Sadegh-Nasseri Scheherazade 

TITLE=H2-O deficiency promotes regulatory T cell differentiation and CD4 T cell hyperactivity

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1304798

DOI=10.3389/fimmu.2023.1304798

ISSN=1664-3224

ABSTRACT=<p>Regulatory T cells (Treg) are crucial immune modulators, yet the exact mechanism of thymic Treg development remains controversial. Here, we present the first direct evidence for H2-O, an MHC class II peptide editing molecular chaperon, on selection of thymic Tregs. We identified that lack of H2-O in the thymic medulla promotes thymic Treg development and leads to an increased peripheral Treg frequency. Single-cell RNA-sequencing (scRNA-seq) analysis of splenic CD4 T cells revealed not only an enrichment of effector-like Tregs, but also activated CD4 T cells in the absence of H2-O. Our data support two concepts; a) lack of H2-O expression in the thymic medulla creates an environment permissive to Treg development and, b) that loss of H2-O drives increased basal auto-stimulation of CD4 T cells. These findings can help in better understanding of predispositions to autoimmunity and design of therapeutics for treatment of autoimmune diseases.</p>