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

Cell Rep. 2023 Jan 31;42(1):111963. doi: 10.1016/j.celrep.2022.111963. Epub 2023 Jan 4.

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 (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.

Keywords: CD8(+) T cell; CP: Immunology; aryl hydrocarbon receptor; cancer immunology; cytotoxicity; development; differentiation; mucosal immunology; tissue resident memory; tumor infiltrating lymphocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes*
  • Cell Differentiation
  • Genome-Wide Association Study
  • Humans
  • Immunologic Memory*
  • Mice
  • Receptors, Aryl Hydrocarbon / genetics

Substances

  • Receptors, Aryl Hydrocarbon