Hue S, Mention JJ, Monteiro RC, Zhang S, Cellier C, Schmitz J et al.. A direct role for NKG2D/MICA interaction in villous atrophy during celiac disease. Immunity 21: 367-377

Equipe Avenir INSERM, Hôpital Necker-Enfants Malades, 75015 Paris, France.
Immunity (Impact Factor: 21.56). 10/2004; 21(3):367-77. DOI: 10.1016/j.immuni.2004.06.018
Source: PubMed


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.

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Available from: Sophie Hüe, Nov 11, 2015
    • "We analyzed phosphorylation of the p38 group of the MAPK ( p38 MAPK ) , by challenging intestinal CACO - 2 cells with our fractions in comparison to the gliadin peptide p31 – 49 , an inducer of innate response in CD mucosa ( Hüe et al . , 2004 ) . We found out that the pro - inflammatory response elicited by fractions 3 and 4 of PT - digested zeins were similar to those of the PT - digested gliadin fractions and to the p31 – 49 for increasing p38 MAPK , as shown in Figure 3 ( A ) . The p38 MAPK participates in a signaling cascade controlling cellular responses , like inflamma"
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    • "The gold standard in the diagnosis of CD is the demonstration of VA in duodenal biopsies [4]. VA is investigated extensively in the medical community [5], [6], [7], and image processing methods as well as quantitative computational methods are highly needed, required and recommended from the community for the characterization of the small intestinal mucosa in suspected and known CD patients [8]. At variance with zoom endoscopy, confocal laser endomicroscopy (CLE) is a relatively novel endoscopic method that permits on-site microscopy of the gastrointestinal mucosa after the application of a fluorescent agent, allowing the experienced endoscopists to diagnose VA, CH as well as intraepithelial lymphocytes with high accuracy [9]. "
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    • "Soluble MIC concentrations were measured in the plasma using a sandwich enzymelinked immunoabsorbent assay as previously described [37]. The detection threshold of recombinant soluble MICA protein , used as standard in each experiment, was 0.1 ng/mL and plasma levels higher than 0.3 ng/mL were considered as positive. "
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