Bcl11b regulates multipotency and effector programs in intestinal resident memory CD8 +T cells

Abstract Tissue-resident memory CD8 +T cells (Trm) reside in non-lymphoid tissues and provide potent protection from re-infection. They are multipotent have diverse functions, including effector roles during Using a series of RNA-seq, ATAC-seq, ChIP-seq CUT&RUN experiments, we investigated Bcl11b-dependent molecular mechanisms governing the differentiation small intestine Trm cells. Mice with conditionally depleted Bcl11b activated had largely altered T cell populations. Particularly their precursors displayed strong transcriptional deregulation. Regions decreased ATAC-seq and/or H3K27ac signal Bcl11b-deficient were enriched for DNA binding motifs associated multifunctional/multipotent program, whereas regions increased program. Correspondingly, genes programs expression cells, respectively. Most program bound by related epigenetic changes These results experimentally validated Tcf1 Ahr, which exhibited at chromatin accessibility, Moreover, impact Tcf1, Blimp1, Ahr alterations on deregulated absence was confirmed rescue experiments. In summary, propose that promotes multipotency restricts programs, is overall essential differentiation. This work supported grants NIH (R01AI067846, R01AI133623) Moffitt Cancer Center (P30CA076292).