The aryl hydrocarbon receptor cell intrinsically promotes resident memory CD8+ T cell differentiation and function
Joseph W. Dean,
Eric Y. Helm,
Zheng Fu,
Lifeng Xiong,
Na Sun,
Kristen N. Oliff,
Marcus Muehlbauer,
Dorina Avram,
Liang Zhou
Affiliations
Joseph W. Dean
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA
Eric Y. Helm
Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL 32608, USA
Zheng Fu
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA
Lifeng Xiong
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA
Na Sun
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA
Kristen N. Oliff
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA
Marcus Muehlbauer
Division of Gastroenterology, Hepatology and Nutrition, College of Medicine, University of Florida, Gainesville, FL 32608, USA
Dorina Avram
Department of Immunology, Moffitt Cancer Center, Tampa, FL 33612, USA
Liang Zhou
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA; Corresponding author
Summary: 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 (TRM) 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+ TRM 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 TRM differentiation and granzyme B production. Collectively, these data suggest that Ahr is an important cell-intrinsic factor for CD8+ T cell immunity.
