2. Academic Validation
  3. Intraepithelial mast cells drive gasdermin C-mediated type 2 immunity

Intraepithelial mast cells drive gasdermin C-mediated type 2 immunity

  • Immunity. 2024 Apr 5:S1074-7613(24)00138-9. doi: 10.1016/j.immuni.2024.03.017.
Liu Yang 1,  Huabin He 2,  Xue-Kun Guo 3,  Jiali Wang 4,  Wenwen Wang 1,  Da Li 2,  Shaonan Liang 4,  Feng Shao 5,  Wanli Liu 6,  Xiaoyu Hu 7
Affiliations

Affiliations

  • 1 Institute for Immunology, Tsinghua University, Beijing, China; School of Basic Medical Sciences, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China.
  • 2 National Institute of Biological Sciences, Beijing, China.
  • 3 Chinese Institutes for Medical Research, Beijing, China.
  • 4 Institute for Immunology, Tsinghua University, Beijing, China; School of Basic Medical Sciences, Tsinghua University, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China.
  • 5 National Institute of Biological Sciences, Beijing, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, China.
  • 6 Institute for Immunology, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China; School of Life Sciences, Tsinghua University, Beijing, China; The State Key Laboratory of Membrane Biology, Beijing, China.
  • 7 Institute for Immunology, Tsinghua University, Beijing, China; School of Basic Medical Sciences, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, Beijing, China; Beijing Key Laboratory for Immunological Research on Chronic Diseases, Beijing, China; The State Key Laboratory of Membrane Biology, Beijing, China. Electronic address: xiaoyuhu@tsinghua.edu.cn.
PMID: 38614091 DOI: 10.1016/j.immuni.2024.03.017
Abstract

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.

Keywords

IL-33; gasdermin C; intestinal epithelium; mast cell; type 2 immunity.

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