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.
Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response / C. Correale, M. Genua, S. Vetrano, E. Mazzini, C. Martinoli, A. Spinelli, V. Arena, L. Peyrin Biroulet, F. Caprioli, N. Passini, P. Panina Bordignon, A. Repici, A. Malesci, S. Rutella, M. Rescigno, S. Danese. - In: GASTROENTEROLOGY. - ISSN 0016-5085. - 144:2(2013 Feb), pp. 346-356.e3.
|Titolo:||Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response|
|Parole Chiave:||Crohn's disease; immune response; mouse model; ulcerative colitis|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
Settore MED/18 - Chirurgia Generale
Settore MED/09 - Medicina Interna
|Data di pubblicazione:||feb-2013|
|Data ahead of print / Data di stampa:||26-ott-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1053/j.gastro.2012.10.040|
|Appare nelle tipologie:||01 - Articolo su periodico|