TREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives

Alessandra Tammaro, Marc Derive, Sebastien Gibot, Jaklien C. Leemans, Sandrine Florquin, Mark C. Dessing

Research output: Contribution to journalReview articleAcademicpeer-review

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. (C) 2017 The Authors. Published by Elsevier Inc
Original languageEnglish
Pages (from-to)81-95
JournalPharmacology & Therapeutics
Volume177
Early online date2017
DOIs
Publication statusPublished - 2017

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