Svensson M, Johansson-Lindbom B, Zapata F, Jaensson E, Austenaa L M, Blomhoff R, Agace W W
Section for Immunology, Lund University, Lund, Sweden.
Mucosal Immunol. 2008 Jan;1(1):38-48. doi: 10.1038/mi.2007.4.
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.
最近的研究突出了肠道树突状细胞（DCs）和维生素A代谢产物视黄酸（RA）在α4β7(+) CCR9(+)“归巢至肠道”效应T细胞生成中的核心作用。在此，我们利用视黄酸反应元件报告基因小鼠证明，脾脏和肠系膜淋巴结（MLN）的DCs均增强了CD8(+) T细胞中的视黄酸受体（RAR）信号传导；然而，只有表达整合素α链CD103的MLN DCs亚群能诱导高效诱导CCR9所需的早期RAR信号。与体内脾脏启动的CD8(+) T细胞相比，MLN启动的CD8(+) T细胞也接收到增强的RAR依赖性信号。在高抗原剂量下，DC介导的肠道归巢受体的进一步诱导受到抑制，而不影响RAR信号传导事件，并导致CD8(+) T细胞进入小肠黏膜的效率降低。这些结果突出了在组织特异性效应T细胞亚群生成过程中抗原剂量与DC亚群诱导的RAR信号传导事件之间复杂的相互作用。
