TY - JOUR
T1 - Retinoic acid receptor signaling levels and antigen dose regulate gut homing receptor expression on CD8(+) T cells
AU - Svensson Frej, Marcus
AU - Johansson Lindbom, Bengt
AU - Zapata, Fernando
AU - Jaensson Gyllenbäck, Elin
AU - Austenaa, L. M.
AU - Blomhoff, R.
AU - Agace, William
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/44349093649
U2 - 10.1038/mi.2007.4
DO - 10.1038/mi.2007.4
M3 - Article
C2 - 19079159
SN - 1933-0219
VL - 1
SP - 38
EP - 48
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 1
ER -