2. Academic Validation
  3. Triggering Receptor Expressed on Myeloid Cells-1 Agonist Regulates Intestinal Inflammation via Cd177+ Neutrophils

Triggering Receptor Expressed on Myeloid Cells-1 Agonist Regulates Intestinal Inflammation via Cd177+ Neutrophils

  • Front Immunol. 2021 Mar 9:12:650864. doi: 10.3389/fimmu.2021.650864.
Dong Hyuk Seo 1 2,  Xiumei Che 1 2,  Soochan Kim 1,  Da Hye Kim 1,  Hyun Woo Ma 1 2,  Jae Hyeon Kim 1 2,  Tae Il Kim 1,  Won Ho Kim 1,  Seung Won Kim 1 2 3,  Jae Hee Cheon 1 2 3
Affiliations

Affiliations

  • 1 Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea.
  • 2 Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
  • 3 Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, South Korea.
PMID: 33767714 DOI: 10.3389/fimmu.2021.650864
Abstract

Triggering receptor expressed on myeloid cell-1 (TREM-1) signaling is expressed on neutrophils and monocytes that is necessary for the successful antimicrobial response and resolution of inflammation in the gut. In this study, we determined the effect of an anti-TREM-1 agonistic antibody (α-TREM-1) on colitis and identify its underlying mechanism of action. Administration of α-TREM-1 alleviated colitis in mice and resolved dysbiosis, which required TLR4/MyD88 signaling. α-TREM-1 increased the production of neutrophil extracellular traps and interleukin-22 by CD177+ neutrophils, which led to pathogen clearance and protection of the intestinal barrier. TREM-1 activation using an α-TREM-1 antibody protects against colitis by rebalancing the microbiota and protecting the epithelium against the immune response as well as modulates the function of neutrophils and macrophages. These results highlight the importance of the TREM-1 pathway in intestinal homeostasis and suggest that α-TREM-1 treatment may be an effective therapeutic strategy for inflammatory bowel disease.

Keywords

CD177; inflammatory bowel disease; macrophage; neutrophil; triggering receptor expressed on myeloid cell.

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