Mesenteric lymph node (mLN) T cells undergo tissue adaptation upon migrating to intestinal lamina propria (LP) and intraepithelial (IE) compartments, ensuring appropriate balance between tolerance and resistance. By combining mouse genetics with single-cell and chromatin analyses, we addressed the molecular imprinting of gut epithelium on T cells. Transcriptionally, conventional and regulatory (Treg) CD4+T cells from mLN, LP and IE segregate based on the gut layer they occupy; trajectory analysis suggests a stepwise loss of CD4-programming and acquisition of an intraepithelial profile. Treg fatemapping coupled with RNA and ATACsequencing revealed that the Treg program shuts down before an intraepithelial program becomes fully accessible at the epithelium. Ablation of CD4 lineagedefining transcription factor ThPOK results in premature acquisition of an IEL profile by mLN Tregs, partially recapitulating epithelium imprinting. Thus, coordinated replacement of circulating lymphocyte program with sitespecific transcriptional and chromatin changes is necessary for tissue imprinting. SOURCE: Daniel Mucida (mucida@mail.rockefeller.edu) - Laboratory of Mucosal Immunology The Rockefeller University

Pluto Bioinformatics

GSE146292: Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program