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

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...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2004-09, Vol.21 (3), p.367-377
Main Authors: Hüe, Sophie, Mention, Jean-Jacques, Monteiro, Renato C., Zhang, ShaoLing, Cellier, Christophe, Schmitz, Jacques, Verkarre, Virginie, Fodil, Nassima, Bahram, Seiamak, Cerf-Bensussan, Nadine, Caillat-Zucman, Sophie
Format: Article
Language:English
Subjects:
Atrophy - immunology
Atrophy - pathology
Celiac disease
Celiac Disease - blood
Celiac Disease - immunology
Celiac Disease - pathology
Cytotoxicity Tests, Immunologic
Enterocytes - immunology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Gliadin - pharmacology
Gluten
HeLa Cells
Humans
Immunohistochemistry
Interleukin-15 - immunology
Intestinal Mucosa - drug effects
Intestinal Mucosa - immunology
Intestinal Mucosa - metabolism
Intestine, Small - immunology
Intestine, Small - pathology
Lymphocytes
NK Cell Lectin-Like Receptor Subfamily K
Protein Biosynthesis
Proteins - drug effects
Proteins - immunology
Receptors, Immunologic - immunology
Receptors, Natural Killer Cell
RNA, Long Noncoding
RNA, Untranslated
Rodents
Small intestine
T-Lymphocytes - immunology
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Summary: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.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2004.06.018