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.
|Journal||Frontiers in Immunology|
|Publication status||Published - 2021 Mar 9|
Bibliographical noteFunding Information:
This research was financially supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HI18C0094); the Mid-Career Researcher Program through a National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP, NRF-2017R1A2B4001848); and an NRF grant funded by the Korean Government (MSIP, NRF-2017R1A1A1A05001011). This work was also supported by the Brain Korea 21 Project for Medical Science, Yonsei University.
© Copyright © 2021 Seo, Che, Kim, Kim, Ma, Kim, Kim, Kim, Kim and Cheon.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy