title: TREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives.
abstract: Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on the majority of innate immune cells and to a lesser extent on parenchymal cells. Upon activation, TREM-1 can directly amplify an inflammatory response. Although it was initially demonstrated that TREM-1 was predominantly associated with infectious diseases, recent evidences shed new light into its role in sterile inflammatory diseases. Indeed, TREM-1 receptor and its signaling pathways contribute to the pathology of several non-infectious acute and chronic inflammatory diseases, including atherosclerosis, ischemia reperfusion-induced tissue injury, colitis, fibrosis and cancer. This review, aims to give an extensive overview of TREM-1 in non-infectious diseases, with the focus on the therapeutic potential of TREM-1 intervention strategies herein. In addition, we provide the reader with a functional enrichment analysis of TREM-1 signaling pathway and potential TREM-1 ligands in these diseases, obtained via in silico approach. We discuss pre-clinical studies which show that TREM-1 inhibition, via synthetic soluble TREM-1 protein mimickers, is effective in treating (preventing) specific inflammatory disorders, without significant effects on antibacterial response. Further research aimed at identifying specific TREM-1 ligands, in different inflammatory disorders, is required to further unravel the role of this receptor, and explore new avenues to modulate its function.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: a.tammaro@amc.uva.nl.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tammaro
authors.affiliation: INOTREM, Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Derive
authors.affiliation: Medical Intensive Care Unit, Hôpital Central, CHU Nancy, Nancy, France; Inserm UMR_S1116, Faculté de Médecine, Université de Lorraine, Nancy, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gibot
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008024:Ligands; D015398:Signal Transduction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: Non-infectious inflammatory diseases; TLR/NLR pathway; TREM-1 inhibitors; TREM-1 ligands; Triggering receptor expressed on myeloid cells-1