TREM1
Description
The TREM1 (triggering receptor expressed on myeloid cells 1) is a protein-coding gene located on chromosome 6.
Triggering receptor expressed on myeloid cells 1 (TREM1) is an immunoglobulin (Ig) superfamily transmembrane protein that, in humans, is encoded by the TREM1 gene. TREM1 is constitutively expressed on the surface of peripheral blood monocytes and neutrophils, and upregulated by toll-like receptor (TLR) ligands; activation of TREM1 amplifies immune responses.
== Function == Monocyte-, macrophage- and neutrophil-mediated inflammatory responses can be stimulated via receptors such as G protein-linked 7-transmembrane receptors (such as FPR1), Fc receptors, CD14, TLRs (such as TLR4), and cytokine receptors. TREM1 amplifies TLR-induced inflammation by increasing production of inflammatory cytokines. The ligand of TREM1 is unknown, however, bacterial infection, ischemic stroke and challenge with lipopolysaccharide or lipoteichoic acid were observed to increase TREM1 expression. In granulocytes, C/EBPε induces TREM1 expression independently from inflammatory response. TREM1 forms a complex with transmembrane adaptor DAP12 and, upon TREM1 engagement, a protein tyrosine kinase Syk-mediated cascade of tyrosine phosphorylation is initiated, activating downstream mediators such as PLCγ, PI3K, and MAPK. This cascade promotes the release of inflammatory cytokines and/or chemokines by neutrophils and macrophages, as well as their migration. Based on laboratory studies, TREM1 might be involved in development of atherosclerosis, non-alcoholic fatty liver disease (NAFLD), and ischemic stroke.
=== Cancer === TREM1 expression is higher in tumor vs non-tumor tissues, likely due to its expression by myeloid cells that infiltrate tumors. TREM1 is expressed by myeloid immune-suppressive cell populations such as monocytic myeloid-derived suppressor cells (mMDSC), tumor-associated neutrophils (TANs), and tumor associated macrophages (TAMs).
[Isoform 1]: Cell surface receptor that plays important roles in innate and adaptive immunity by amplifying inflammatory responses (PubMed:10799849, PubMed:21393102). Upon activation by various ligands such as PGLYRP1, HMGB1 or HSP70, multimerizes and forms a complex with transmembrane adapter TYROBP/DAP12 (PubMed:25595774, PubMed:17568691, PubMed:29568119). In turn, initiates a SYK-mediated cascade of tyrosine phosphorylation, activating multiple downstream mediators such as BTK, MAPK1, MAPK3 or phospholipase C-gamma (PubMed:21659545, PubMed:14656437). This cascade promotes the neutrophil- and macrophage- mediated release of pro-inflammatory cytokines and/or chemokines, as well as their migration and thereby amplifies inflammatory responses that are triggered by bacterial and fungal infections (PubMed:17568691, PubMed:17098818). By also promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptor (TLR) and NOD-like receptor engagement, plays a major role in the pathophysiology of acute and chronic inflammatory diseases of different etiologies including septic shock and atherosclerosis (PubMed:21393102, PubMed:11323674). {ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:11323674, ECO:0000269|PubMed:14656437, ECO:0000269|PubMed:17098818, ECO:0000269|PubMed:17568691, ECO:0000269|PubMed:21393102, ECO:0000269|PubMed:21659545, ECO:0000269|PubMed:25595774, ECO:0000269|PubMed:29568119}
TREM1 is also known as CD354, TREM-1.
