Immunity
Volume 21, Issue 3, September 2004, Pages 367-377
Journal home page for Immunity

Article
A Direct Role for NKG2D/MICA Interaction in Villous Atrophy during Celiac Disease

https://doi.org/10.1016/j.immuni.2004.06.018Get rights and content
Under an Elsevier user license
open archive

Abstract

MICA molecules interact with the NKG2D-activating receptor on human NK and CD8 T cells. We investigated the participation of the MICA/NKG2D pathway in the destruction of intestinal epithelium by intraepithelial T lymphocytes (IEL) in Celiac disease and its premalignant complication, refractory sprue. We show that MICA is strongly expressed at epithelial cell surface in patients with active disease and is induced by gliadin or its p31-49 derived peptide upon in vitro challenge, an effect relayed by IL-15. This triggers direct activation and costimulation of IEL through engagement of NKG2D, leading to an innate-like cytotoxicity toward epithelial targets and enhanced TCR-dependent CD8 T cell-mediated adaptive response. Villous atrophy in Celiac disease might thus be ascribed to an IEL-mediated damage to enterocytes involving NKG2D/MICA interaction after gliadin-induced expression of MICA on gut epithelium. This supports a key role for MIC/NKG2D in the activation of intraepithelial immunity in response to danger.

Cited by (0)

7

Present address: Department of Endocrinology, Second Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510275, China.