Intraepithelial mast cells drive gasdermin C-mediated type 2 immunity.
Immunity
; 57(5): 1056-1070.e5, 2024 May 14.
Article
in En
| 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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Phosphate-Binding Proteins
/
Interleukin-33
/
Mast Cells
Limits:
Animals
Language:
En
Year:
2024
Type:
Article