Retinoic acid receptor signaling levels and antigen dose regulate gut homing receptor expression on CD8+ T cells.
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.
Svensson
M
M
Section for Immunology, Lund University, Lund, Sweden.
Johansson-Lindbom
B
B
Zapata
F
F
Jaensson
E
E
Austenaa
L M
LM
Blomhoff
R
R
Agace
W W
WW
D000818:Animals; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D039001:Integrin alpha Chains / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000276:immunology; D054388:Receptors, CCR / Q000276:immunology; D018168:Receptors, Retinoic Acid / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000941:Antigens; D015703:Antigens, CD; C119309:CC chemokine receptor 9; D039001:Integrin alpha Chains; D054388:Receptors, CCR; D018168:Receptors, Retinoic Acid; C091367:alpha E integrins