title: Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Correale
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Genua
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Vetrano
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Mazzini
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Martinoli
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Spinelli
authors.affiliation: Department of Pathology, Catholic University Medical School, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Arena
authors.affiliation: Department of Gastroenterology, Inserm U954, University Hospital of Nancy, Henri Poincaré University, Vandœuvre-lès-Nancy, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
authors.affiliation: U.O. Gastroenterologia 2, Fondazione IRCCS Ca' Granda Ospedale Policlinico di Milano, Milan, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Caprioli
authors.affiliation: Bioxell, Milan, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Passini
authors.affiliation: Reproductive Sciences Lab, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Panina-Bordignon
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Repici
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Malesci
authors.affiliation: Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.affiliation: Department of Experimental Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Rescigno
authors.affiliation: Division of Gastroenterology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: sdanese@hotmail.com.
authors.forename: Silvio
authors.initials: S
authors.lastname: Danese
mesh_terms: D000818:Animals; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011971:Receptors, Immunologic / Q000096:biosynthesis*
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human; C498716:Trem2 protein, mouse