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

Dong Hyuk Seo; Xiumei Che; Soochan Kim; Da Hye Kim; Hyun Woo Ma; Jae Hyeon Kim; Tae Il Kim; Won Ho Kim; Seung Won Kim; Jae Hee Cheon

doi:10.3389/fimmu.2021.650864

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

Dong Hyuk Seo, Xiumei Che, Soochan Kim, Da Hye Kim, Hyun Woo Ma, Jae Hyeon Kim, Tae Il Kim, Won Ho Kim, Seung Won Kim, Jae Hee Cheon

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

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.

Original language	English
Article number	650864
Journal	Frontiers in Immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.650864
Publication status	Published - 2021 Mar 9

Bibliographical note

Funding 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.

Publisher Copyright:
© Copyright © 2021 Seo, Che, Kim, Kim, Ma, Kim, Kim, Kim, Kim and Cheon.

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

Access to Document

10.3389/fimmu.2021.650864

Cite this

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

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.",

author = "Seo, {Dong Hyuk} and Xiumei Che and Soochan Kim and Kim, {Da Hye} and Ma, {Hyun Woo} and Kim, {Jae Hyeon} and Kim, {Tae Il} and Kim, {Won Ho} and Kim, {Seung Won} and Cheon, {Jae Hee}",

note = "Funding 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. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Seo, Che, Kim, Kim, Ma, Kim, Kim, Kim, Kim and Cheon.",

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AU - Seo, Dong Hyuk

AU - Che, Xiumei

AU - Kim, Soochan

AU - Kim, Da Hye

AU - Ma, Hyun Woo

AU - Kim, Jae Hyeon

AU - Kim, Tae Il

AU - Kim, Won Ho

AU - Kim, Seung Won

AU - Cheon, Jae Hee

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PY - 2021/3/9

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N2 - 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.

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