Emerging roles for triggering receptor expressed on myeloid cells receptor family signaling in inflammatory diseases

作者：Pelham Christopher J; Agrawal Devendra K^*

来源：Expert Review of Clinical Immunology, 2014, 10(2): 243-256.

DOI：10.1586/1744666X.2014.866519

• 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

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 %26apos;amplifier%26apos; 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.

• 出版日期2014-2