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

Svensson Frej, Marcus LU ; Johansson Lindbom, Bengt LU ; Zapata, Fernando LU ; Jaensson Gyllenbäck, Elin LU ; Austenaa, L. M.; Blomhoff, R. and Agace, William LU (2008) In Mucosal Immunology 1(1). p.38-48
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Mucosal Immunology
volume
1
issue
1
pages
38 - 48
publisher
Nature Publishing Group
external identifiers
  • wos:000260408400007
  • pmid:19079159
  • scopus:44349093649
ISSN
1933-0219
DOI
10.1038/mi.2007.4
language
English
LU publication?
yes
id
e88a8cff-8339-4519-996e-8ef011ca23bf (old id 1283863)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19079159?dopt=Abstract
date added to LUP
2009-02-09 11:17:20
date last changed
2017-10-22 03:51:24
@article{e88a8cff-8339-4519-996e-8ef011ca23bf,
  abstract     = {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.},
  author       = {Svensson Frej, Marcus and Johansson Lindbom, Bengt and Zapata, Fernando and Jaensson Gyllenbäck, Elin and Austenaa, L. M. and Blomhoff, R. and Agace, William},
  issn         = {1933-0219},
  language     = {eng},
  number       = {1},
  pages        = {38--48},
  publisher    = {Nature Publishing Group},
  series       = {Mucosal Immunology},
  title        = {Retinoic acid receptor signaling levels and antigen dose regulate gut homing receptor expression on CD8(+) T cells},
  url          = {http://dx.doi.org/10.1038/mi.2007.4},
  volume       = {1},
  year         = {2008},
}