Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany.
Directors' Research Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany.
Front Immunol. 2022 Feb 3;13:812899. doi: 10.3389/fimmu.2022.812899. eCollection 2022.
Organized intestinal mucosal immune response appears to be restricted to tetrapods. In teleost fish, there is no evidence for the existence of a particular intestinal region that facilitates the interaction of antigen-presenting cells (APCs) and T cells, such as secondary lymphoid organs. Indeed, despite their importance in the defense against pathogens, the location and manner of APC-T cell interaction within the fish gut is unknown. Here, using non-invasive live imaging of newly developed transgenic reporter lines, we addressed the spatial organization and behavior of APCs and T cells in the intestine of medaka fish both during homeostasis and inflammation. We report that Ccr9a T cells are recruited to a band in the lamina propria next to the muscularis mucosa in which Ccl25-expressing cells are present. Ccr9a T cells contact APCs for several minutes, in a process mediated by connexin 43. This type of interaction was observed in homeostasis and inflammation, with the interaction being longer and more frequent during inflammation. Thus, our results demonstrate that the mucosal immune response in the intestine of medaka is organized and endowed with a specific region with specialized microenvironment and function.
组织化的肠道黏膜免疫反应似乎仅限于四足动物。在硬骨鱼中，没有证据表明存在有利于抗原呈递细胞 (APC) 和 T 细胞相互作用的特定肠道区域，如次级淋巴器官。事实上，尽管它们在抵御病原体方面很重要，但鱼类肠道中 APC-T 细胞相互作用的位置和方式尚不清楚。在这里，我们使用新开发的转基因报告系的非侵入性活体成像，研究了在稳态和炎症期间，黄颡鱼肠道中 APC 和 T 细胞的空间组织和行为。我们报告说，Ccr9a T 细胞被募集到固有层中的一条带中，该带紧邻黏膜肌层，其中存在表达 Ccl25 的细胞。Ccr9a T 细胞与 APC 接触数分钟，这一过程由连接蛋白 43 介导。这种相互作用在稳态和炎症中都观察到，在炎症期间，相互作用时间更长、更频繁。因此，我们的结果表明，黄颡鱼肠道中的黏膜免疫反应是有组织的，并具有特定的区域，具有专门的微环境和功能。
