The aryl hydrocarbon receptor cell intrinsically promotes resident memory CD8(+) T cell differentiation and function

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(RM)) differentiation and function. Genetic ablation of Ahr in mouse CD8(+) T cells leads to increased CD127(−)KLRG1(+) short-lived effector cells and CD44(+)CD62L(+) T central memory cells but reduced granzyme-B-producing CD69(+)CD103(+) T(RM) 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(RM) differentiation and granzyme B production. Collectively, these data suggest that Ahr is an important cell-intrinsic factor for CD8(+) T cell immunity.