Retinoic acid receptor signaling levels and antigen dose regulate gut homing receptor expression on CD8+ T cells

Mucosal Immunol. 2008 Jan;1(1):38-48. doi: 10.1038/mi.2007.4.

Abstract

Recent studies have highlighted a central role for intestinal dendritic cells (DCs) and vitamin A metabolite retinoic acid (RA) in the generation of alpha4beta7(+) CCR9(+)"gut tropic" effector T cells. Here, using RA-responsive element reporter mice, we demonstrate that both splenic and mesenteric lymph node (MLN) DCs enhanced retinoic acid receptor (RAR) signaling in CD8(+) T cells; however, only a subset of MLN DCs, expressing the integrin alpha-chain CD103, induced an early RAR signal that is required for efficient CCR9 induction. MLN-primed CD8(+) T cells also received enhanced RAR-dependent signals compared with splenic-primed CD8(+) T cells in vivo. Further DC-mediated induction of gut homing receptors was inhibited at a high antigen dose without influencing RAR signaling events, and resulted in less efficient CD8(+) T-cell entry into the small intestinal mucosa. These results highlight a complex interplay between antigen dose and DC subset-induced RAR signaling events in the generation of tissue tropic effector T-cell subsets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology*
  • Antigens, CD / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Immunologic
  • Integrin alpha Chains / immunology
  • Intestinal Mucosa / immunology*
  • Intestine, Small / immunology
  • Mice
  • Mice, Transgenic
  • Organ Specificity / immunology
  • Receptors, CCR / immunology
  • Receptors, Retinoic Acid / immunology*
  • Signal Transduction / immunology*
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antigens
  • Antigens, CD
  • CC chemokine receptor 9
  • Integrin alpha Chains
  • Receptors, CCR
  • Receptors, Retinoic Acid
  • alpha E integrins