A specialized population of mast cells residing within epithelial layers, currently known as intraepithelial mast cells (IEMCs), was originally observed over a century ago, yet their physiological functions have remained enigmatic. In this study, we unveil an unexpected and crucial role of IEMCs in driving gasdermin C-mediated type 2 immunity. During helminth infection, αEβ7 integrin-positive IEMCs engaged in extensive intercellular crosstalk with neighboring intestinal epithelial cells (IECs). Through the action of IEMC-derived proteases, gasdermin C proteins intrinsic to the epithelial cells underwent cleavage, leading to the release of a critical type 2 cytokine, interleukin-33 (IL-33). Notably, mast cell deficiency abolished the gasdermin C-mediated immune cascade initiated by epithelium. These findings shed light on the functions of IEMCs, uncover a previously unrecognized phase of type 2 immunity involving mast cell-epithelial cell crosstalk, and advance our understanding of the cellular mechanisms underlying gasdermin C activation.

中文翻译：

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上皮内肥大细胞驱动gasdermin C介导的2型免疫

上皮层内肥大细胞的特殊群体，目前称为上皮内肥大细胞（IEMC），最初在一个多世纪前就被观察到，但它们的生理功能仍然是个谜。在这项研究中，我们揭示了 IEMC 在驱动 Gasdermin C 介导的 2 型免疫中发挥的意想不到的关键作用。在蠕虫感染期间，αEβ7 整合素阳性 IEMC 与邻近的肠上皮细胞 (IEC) 进行广泛的细胞间串扰。通过 IEMC 衍生蛋白酶的作用，上皮细胞固有的 Gasdermin C 蛋白发生裂解，导致关键的 2 型细胞因子白细胞介素 33 (IL-33) 的释放。值得注意的是，肥大细胞缺陷消除了由上皮细胞启动的gasdermin C介导的免疫级联反应。这些发现揭示了 IEMC 的功能，揭示了之前未被识别的涉及肥大细胞-上皮细胞串扰的 2 型免疫阶段，并增进了我们对 Gasdermin C 激活的细胞机制的理解。