title: Triggering receptor expressed on myeloid cells receptor family modulators: a patent review.
abstract: BACKGROUND
  Triggering receptor expressed on myeloid cells (TREM) receptors and TREM-like transcript (TLT; or TREML) receptors of the immunoglobulin superfamily are known as key modulators of host immune responses. TREM-1 (CD354) and TREM-2 share the transmembrane adaptor DNAX-activation protein of 12 kDa (DAP12), but they possess separate stimulatory and inhibitory functional roles, especially in myeloid cells.
  
  
  METHODS
  This review covers findings related to TREMs and TLTs published in patent applications from their discovery in 2000 to the present. New roles for TREM-1, TREM-2, TLT-1 and TLT-2 in maladies ranging from acute and chronic inflammatory disorders to cardiovascular diseases and cancers are discussed. Putative endogenous ligands and novel synthetic peptide blockers are also discussed.
  
  
  CONCLUSIONS
  So far, therapeutic use of activators/blockers specific for TREMs and TLTs has been limited to preclinical animal models. TREM-1 is an immediate therapeutic target for acute and chronic inflammatory conditions, especially sepsis. Certain mutations in DAP12 and TREM-2 manifest into a disorder named polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, and newly identified TREM-2 variants confer a significant increase in risk of developing Alzheimer's disease. This makes TREM-2 an attractive therapeutic target for neurodegenerative diseases.
authors.affiliation: Creighton University School of Medicine, Department of Biomedical Sciences and Center for Clinical & Translational Science , Omaha, NE 68178 , USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Pelham
authors.forename: Amit N
authors.initials: AN
authors.lastname: Pandya
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D000818:Animals; D006801:Humans; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000502:physiology; D010330:Patents as Topic; D011971:Receptors, Immunologic / Q000187:drug effects* / Q000502:physiology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C424124:TREM-2a receptor; C424125:TREM-2b receptor; C408842:TREM1 protein, human; C473366:TREML1 protein, human; C000591058:TREML4 protein, human; C447602:Trem3 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: CD177; DNAX activation protein of 12 kDa; TREM-like transcript; heat shock protein 60; high-mobility group box 1; immunomodulator; peptidoglycan recognition protein 1; toll-like receptor; triggering receptor expressed on myeloid cells