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

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Author

Summary, in English

Recent studies have highlighted a central role for intestinal dendritic cells (DCs) and vitamin A metabolite retinoic acid (RA) in the generation of alpha 4 beta 7(+) 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.

Department/s

  • Immunology

Publishing year

2008

Language

English

Pages

38-48

Publication/Series

Mucosal Immunology

Volume

1

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Immunology in the medical area

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1933-0219