- 作者: Fu-Chen Yang, Po-Yuan Chiu, Yun Chen, Tak W. Mak and Nien-Jung Chen
- 作者服務機構: 1. Institute of Microbiology and Immunology, School of Life Sciences, National Yang-Ming University, No.155, Sec.2, Linong Street, Taipei, Taiwan 2. Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan 3. The Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, University Health Network and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, M5G 2C1, Canada 4. Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan
- 中文摘要:
- 英文摘要:
Background
Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed on macrophages in inflamed intestines and reportedly promotes inflammatory bowel disease (IBD) by augmenting pro-inflammatory responses. To study the mechanism mediated by TREM-1 on macrophages, we generated an independent TREM-1 deficient mouse.
Methods
Acute colitis was induced in C57BL/6 and TREM-1-deficient mice by the administration of dextran sodium sulfate (DSS). Colonic lamina propria immune cell composition and cytokines were analyzed. An innate lymphoid cell (ILC) co-culture experiment with macrophages was used to analyze IL-22 levels. Exogenous IL-22 and TREM-1-expressing macrophages were supplied to TREM-1-deficient mice for examining their effects on intestinal barrier integrity.
Results
In inflamed colons, TREM-1 loss compromised the activation of ILC3 and their production of IL-22, which is required for intestinal barrier integrity. ILC3-mediated IL-22 production depends on IL-1β secreted by M1-polarized macrophages, and we found that TREM-1 deficiency results in a decreased number of IL-1β producing-M1 macrophages in colons exposed to DSS. Accordingly, DSS-mediated damage was ameliorated by supplying exogenous IL-22 and TREM-1-expressing macrophages to TREM-1-deficient mice.
Conclusions
TREM-1 plays a crucial role in regulating IL-22 production by ILC3 through modulating M1-macrophage polarization during DSS-induced acute colitis. - 中文關鍵字:
- 英文關鍵字: Triggering expressed on myeloid cells-1, Inflammatory macrophages, IL-22, Group 3 innate lymphoid cells, Colitis