Dean J. W. et al.
The Aryl hydrocarbon receptor (Ahr) regulates the differentiation and function of CD4 T cells; however, its cell-intrinsic role in CD8 T cells remains elusive. Herein we show that Ahr acts as a promoter of resident memory CD8 T cell (T) differentiation and function. Genetic ablation of Ahr in mouse CD8 T cells leads to increased CD127KLRG1 short-lived effector cells and CD44CD62L T central memory cells but reduced granzyme-B-producing CD69CD103 T cells. Genome-wide analyses reveal that Ahr suppresses the circulating while promoting the resident memory core gene program. A tumor resident polyfunctional CD8 T cell population, revealed by single-cell RNA-seq, is diminished upon Ahr deletion, compromising anti-tumor immunity. Human intestinal intraepithelial CD8 T cells also highly express AHR that regulates in vitro T differentiation and granzyme B production. Collectively, these data suggest that Ahr is an important cell-intrinsic factor for CD8 T cell immunity.