Intraepithelial mast cells drive gasdermin C-mediated type 2 immunity.
Immunity
; 57(5): 1056-1070.e5, 2024 May 14.
Article
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| MEDLINE
| ID: mdl-38614091
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, αEß7 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Unión a Fosfato
/
Proteínas Citotóxicas Formadoras de Poros
/
Interleucina-33
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Mastocitos
Límite:
Animals
Idioma:
En
Año:
2024
Tipo del documento:
Article