The aryl hydrocarbon receptor cell intrinsically promotes resident memory CD8+ T cell differentiation and function
Joseph Dean, Eric Y. Helm, Zheng Fu, Lifeng Xiong, Na Sun, Kristen N. Oliff, Marcus Muehlbauer, Dorina Avram, Liang Zhou
Abstract
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.