TREM1

Monocyte/macrophage- and neutrophil-mediated inflammatory responses can be stimulated through a variety of receptors, including G protein-linked 7-transmembrane receptors (e.g., FPR1), Fc receptors, CD14, Toll-like receptors (TLRs; e.g., TLR4), and cytokine receptors. TREM-1 amplifies toll-like receptors induced inflammation by further increasing the production of proinflammatory cytokines.[8] The ligand of TREM-1 is unknown, however, bacterial infection, ischemic stroke and challenge with lipopolysaccharide or lipoteichoic acid were observed to increase TREM-1 expression.[9] In granulocyte cells, C/EBPε was also shown to induce TREM-1 expression independently from inflammatory response.[10]

Interpreted from laboratory studies, TREM-1 may have a role in development of atherosclerosis,[11] non-alcoholic fatty liver disease,[12] and ischemic stroke.[13]

During inflammation, a soluble form of the molecule (sTREM-1) accumulates in the circulation, that is used as a biomarker to indicate inflammation. It is a matter of debate whether sTREM-1 is produced as a splice variant or as the results of proteolytic cleavage, but studies found evidence for both mechanisms.[14][15] sTREM-1 acts as a decoy receptor by competing for the unknown TREM-1 ligand. Therefore it provides a negative feedback loop for TREM-1 activation.[16] sTREM-1 has been demonstrated to provide valuable information about the extent of inflammatory processes and/or outcomes in the context of pneumonia,[17] sepsis,[18] inflammatory bowel disease[19][20] and liver cirrhosis.[21]

Model organisms have been used in the study of TREM1 function. A conditional knockout mouse line called Trem1^{tm1(KOMP)Vlcg} was generated at the Wellcome Trust Sanger Institute.[22] Male and female animals underwent a standardized phenotypic screen[23] to determine the effects of deletion.[24][25][26][27] Additional screens performed: - In-depth immunological phenotyping[28]