Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ 07101, USA; Department of Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ 07101, USA.
Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ 07101, USA; Department of Pathology, Immunology, and Laboratory Medicine, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ 07101, USA.
Cell Rep. 2022 Aug 2;40(5):111150. doi: 10.1016/j.celrep.2022.111150.
Intestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A adenosine receptor (AAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC AAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.
肠道线虫寄生虫可以穿过上皮屏障，导致组织损伤和危险相关分子模式 (DAMPs) 的释放，这可能促进宿主保护性 2 型免疫。我们研究了腺苷与肠道上皮细胞 (IEC) 上的 A 腺苷受体 (AAR) 结合是否发挥重要作用。IEC AAR 的特异性阻断抑制了宿主对肠道蠕虫 Heligmosomoides polygyrus bakeri (Hpb) 的保护性记忆反应，包括破坏宿主-寄生虫界面的肉芽肿发育。在初次反应期间，记忆 T 细胞的发育被阻断，转录分析显示 IEC 激活受到严重损害。接种后 24 小时可视化细胞外 ATP，并在 CD39 缺陷小鼠中表明，细胞外 ATP 对于介导 2 型免疫起始的腺苷产生至关重要。我们的研究表明，一种有效的腺苷介导的 IEC 途径与绒毛细胞回路一起，对 2 型免疫的激活至关重要。
