Novel ligands and modulators of triggering receptor expressed on myeloid cells receptor family: 2015-2020 updates

ABSTRACT

Introduction: Triggering receptors expressed on myeloid cells (TREMs) are inflammatory amplifiers with defined pathophysiological role in various infectious diseases, acute and chronic aseptic inflammations, and a variety of cancers, depicting TREMs as prominent therapeutic targets.

Areas covered: Herein, updates from 2015 to 2020 are discussed to divulge the TREM ligands, as well as their peptide blockers, claimed to modulate their expression. The article also presents different strategies employed during the last five years to block interactions between TREMs and their ligands to treat various disease conditions by modulating their expression and activity.

Expert opinion: There has been significant progress in the discovery of novel ligands and modulators of TREMs in the last five years that mainly revolved around the function of TREM molecules. A few peptides showed encouraging results to modulate the expression and activity of TREMs in preclinical studies, and these peptides are currently under clinical investigation. Based on the findings so far in several careful studies, we expect novel therapeutics in the near future which could have the ability to treat various disease conditions associated with TREM expression.

KEYWORDS:

• ADAMs
• arthritis
• atherosclerosis
• dap12
• eCIRP
• extracellular actin
• hmgb-1
• hsp70
• infectious diseases
• pglyrp1
• sepsis
• trem-1
• trem-2
• trem-like transcripts
• TREM modulators

Article highlights

• Various TREM ligands, which can modulate TREM expression have been identified within last five years (2015-2020).

• Several TREM-1 and TREM-2 modulators are currently under evaluation in preclinical and clinical studies of many inflammatory diseases.

• Multiple strategies employed in the modulation of TREM-1 and TREM-2 expression have been presented.

• TREM-1 and TREM-2 and their soluble receptors in patients’ samples could be used as biomarkers to monitor clinical progression in several diseases.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial or non-financial involvement with any organization or entity with financial or non-financial interest or conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are an employee of Denali therapeutics and they are developing antibodies targeting Trem2. All other peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The research work of DK Agrawal is supported by research grants R01 HL144125 and R01HL147662 from the National Institutes of Health, USA. The content of this review article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.