• Gastroenterology · Feb 2013

    Comparative Study

    Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response.

    • Carmen Correale, Marco Genua, Stefania Vetrano, Elisa Mazzini, Chiara Martinoli, Antonino Spinelli, Vincenzo Arena, Laurent Peyrin-Biroulet, Flavio Caprioli, Nadia Passini, Paola Panina-Bordignon, Alessandro Repici, Alberto Malesci, Sergio Rutella, Maria Rescigno, and Silvio Danese.
    • Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
    • Gastroenterology. 2013 Feb 1;144(2):346-356.e3.

    Background And AimsTriggering receptor expressed on myeloid cells (TREM)-2 is a surface receptor detected on macrophages, dendritic cells, and microglia that binds repeated anionic motifs on yeast and Gram-positive and Gram-negative bacteria. Little is known about TREM-2 expression and function in the intestine or its role in inflammatory bowel disease (IBD). We investigated the expression of TREM-2 in the intestinal lamina propria and its role in the development of colonic inflammation.MethodsWe measured levels of TREM-2 in lamina propria mononuclear cells from surgical specimens collected from patients with IBD or cancer (controls). We analyzed the development of colitis in TREM-2 knockout and wild-type mice. Colon samples were isolated from mice and analyzed for cytokine expression, phagocytosis of bacteria, proliferation in colonic crypts, lamina propria mononuclear cell function, and T-cell activation by ovalbumin.ResultsTREM-2 was virtually absent from colon samples of control patients, but levels were significantly higher in within the inflamed mucosa of patients with IBD; it was mainly expressed by CD11c(+) cells. Levels of TREM-2 increased as acute or chronic colitis was induced in mice. TREM-2 knockout mice developed less severe colitis than wild-type mice; the knockout mice lost less body weight, had a lower disease activity index, and had smaller mucosal lesions in endoscopic analysis. Colon dendritic cells from TREM-2 knockout mice produced lower levels of inflammatory cytokines and had reduced levels of bacterial killing and T-cell activation than cells from wild-type mice.ConclusionsTREM-2 contributes to mucosal inflammation during development of colitis in mice. Levels of TREM-2 are increased within the inflamed mucosa of patients with IBD, indicating its potential as a therapeutic target.Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

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