Bcl11b sustains multipotency and restricts effector programs of intestinal-resident memory CD8 + T cells

• DOI: 10.1126/sciimmunol.abn0484
• Publication Date: 2023-04-28T17:58:06Z
• Authors: Eric Y. Helm; Tomas Zelenka; Valeriu B. Cismasiu; Shamima Islam; Leonardo Silvane; Beatrice Zitti; Tim D. Holmes; Theodore T. Drash...; Alexander J. Kwia...; Christine Tao; Joseph Dean; Alyssa N. Obermayer; Xianghong Chen; Benjamin G. Kesel...; Weizhou Zhang; Zhiguang Huo; Liang Zhou; Brian S. Sheridan; Jose R. Conejo-Ga...; Timothy I. Shaw; Yenan T. Bryceson; Dorina Avram
• Keywords: Intestines; Repressor Proteins; Mice; Tumor Suppressor Proteins; Animals; Cell Differentiation; CD8-Positive T-Lymphocytes; Transcription Factors

The networks of transcription factors (TFs) that control intestinal-resident memory CD8 + T (T RM ) cells, including multipotency and effector programs, are poorly understood. In this work, we investigated the role TF Bcl11b in cells during infection with Listeria monocytogenes using mice post-activation, conditional deletion cells. Conditional resulted increased numbers intestinal their precursors as well decreased splenic circulating precursors. Loss was part due to homing −/− precursors, no major alterations programs. had altered transcriptional diminished expression multipotent/multifunctional (MP/MF) program genes, Tcf7 , up-regulation Prdm1. also limits Ahr, another a cell differentiation. Deregulation programs translated into poor recall response despite accumulation intestine. Reduced MP/MF genes linked chromatin accessibility reduction activating histone marks at these loci. contrast, displayed epigenetic status. These findings demonstrate is frontrunner tissue residency upstream Tcf1 Blimp1, promoting restricting program.