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The Aryl Hydrocarbon Receptor Cell-Intrinsically Promotes Resident Memory CD8+ T Cell Differentiation and Function

ABSTRACT: The Aryl hydrocarbon receptor (Ahr) regulates the differentiation and function of CD4+ T cells; however, the cell-intrinsic role of Ahr in CD8+ T cells, remains elusive. Herein we show that Ahr acts as a promoter of resident memory CD8+ T cell (TRM) differentiation and function. Under steady state conditions or in an oral infection model, genetic ablation of Ahr in CD8+ T cells leads to an increase in CD127–KLRG1+ short lived effector cells (TSLE) and CD44+CD62L+ T central memory (TCM) cells, but a reduction in Granzyme B-producing CD69+CD103+ T resident memory (TRM) cells. Genome-wide transcriptome and cistrome analyses reveal that Ahr suppresses the circulating while promoting the resident memory core gene program. A tumor resident polyfunctional CD8+ T cell population dependent on Ahr is revealed by single cell RNA-Seq, and deletion of Ahr in CD8+ T cells compromises anti-tumor immunity. Consistent with mouse, human IEL CD8+ T cells highly express AHR that regulates in vitro TRM differentiation and Granzyme B production. Collectively, these data suggest that Ahr is an important cell-intrinsic factor for CD8+ T cell immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE220944 | GEO | 2023/01/11

REPOSITORIES: GEO

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