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Bacterial Sensor Triggering Receptor Expressed on Myeloid Cells-2 Regulates the Mucosal Inflammatory Response

Abstract : Background and Aims Triggering 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. Methods We 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. Results TREM-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. Conclusions TREM-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.
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Submitted on : Monday, February 5, 2018 - 2:37:17 PM
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Carmen Correale, Marco Genua, Stefania Vetrano, Elisa Mazzini, Chiara Martinoli, et al.. Bacterial Sensor Triggering Receptor Expressed on Myeloid Cells-2 Regulates the Mucosal Inflammatory Response. Gastroenterology, Elsevier, 2013, 144 (2), pp.346 - 356.e3. ⟨10.1053/j.gastro.2012.10.040⟩. ⟨hal-01700971⟩



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