TY - JOUR
T1 - Emerging roles for triggering receptor expressed on myeloid cells receptor family signaling in inflammatory diseases
AU - Pelham, Christopher J.
AU - Agrawal, Devendra K.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
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U2 - 10.1586/1744666X.2014.866519
DO - 10.1586/1744666X.2014.866519
M3 - Review article
C2 - 24325404
AN - SCOPUS:84893072503
VL - 10
SP - 243
EP - 256
JO - Expert Review of Clinical Immunology
JF - Expert Review of Clinical Immunology
SN - 1744-666X
IS - 2
ER -