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+ Tcells; however, its cell-intrinsic role in CD8+ Tcells remains elusive. Herein we show that Ahr acts as a promoter of resident memory CD8+ Tcell (TRM) differentiation and function. Genetic ablation of Ahr in mouse CD8+ Tcells leads to increased CD127-KLRG1+ short-lived effector cells and CD44+CD62L+ T central memory cells but reduced granzyme-B-producing CD69+CD103+ TRM cells. Genome-wide analyses reveal that Ahr suppresses the circulating while promoting the resident memory core gene program. A tumor resident polyfunctional CD8+ Tcell population, revealed by single-cell RNA-seq, is diminished upon Ahr deletion, compromising anti-tumor immunity. Human intestinal intraepithelial CD8+ Tcells also highly express AHR that regulates invitro TRM differentiation and granzyme B production. Collectively, these data suggest that Ahr is an important cell-intrinsic factor for CD8+ Tcell immunity.