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

In English

Författare

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.

Avdelning/ar

  • Immunology

Publiceringsår

2008

Språk

Engelska

Sidor

38-48

Publikation/Tidskrift/Serie

Mucosal Immunology

Volym

1

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Nature Publishing Group

Ämne

  • Immunology in the medical area

Status

Published

Forskningsgrupp

  • Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1933-0219