Emerging roles for triggering receptor expressed on myeloid cells receptor family signaling in inflammatory diseases. (February 2014)

• Record Type: Journal Article
• Authors: Pelham, Christopher J; Agrawal, Devendra K
• Is Part Of: Expert review of clinical immunology. Volume 10:Number 2(2014)
• Page Start: 243
• Page End: 256
• Publication Date: 2014-02
• Subjects: cardiovascular disease -- DNAX activation protein of 12 kDa -- high-mobility group box 1 -- inflammation -- metabolic syndrome -- Toll-like receptors -- triggering receptor expressed on myeloid cells; Clinical immunology -- Periodicals; 616.079
• DOI: 10.1586/1744666X.2014.866519
• Languages: English
• ISSNs: 1744-666X

Abstract

Abstract : Innate immune receptors represent important therapeutic targets for inflammatory disorders. In particular, the Toll-like receptor (TLR) family has emerged as a promoter of chronic inflammation that contributes to obesity, insulin resistance and atherosclerosis. Importantly, triggering receptor expressed on myeloid cells-1 (TREM-1) has been characterized as an 'amplifier' of TLR2 and TLR4 signaling. TREM-1- and TREM-2-dependent signaling, as opposed to TREM-like transcript-1 (TLT-1 or TREML1), are mediated through association with the transmembrane adaptor DNAX activation protein of 12 kDa (DAP12). Recessive inheritance of rare mutations in DAP12 or TREM-2 results in a disorder called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, and surprisingly these subjects are not immunocompromised. Recent progress into the roles of TREM/DAP12 signaling is critically reviewed here with a focus on metabolic, cardiovascular and inflammatory diseases. The expanding repertoire of putative ligands for TREM receptors is also discussed.