Abstract
BackgroundTriggering 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.MethodsAcute 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.ResultsIn 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.ConclusionsTREM-1 plays a crucial role in regulating IL-22 production by ILC3 through modulating M1-macrophage polarization during DSS-induced acute colitis.
Highlights
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
TREM-1 deficiency exacerbates dextran sodium sulfate (DSS)-induced colitis Previous studies have demonstrated that increased expression of TREM-1 on colonic macrophages is an important indicator of colonic inflammation in both mice and humans [12]
Because IL1β is a potent inducer of IL-22 production by ILC3 cells, these results suggest a novel mechanism by which TREM-1 can protect the intestine from DSS-induced epithelial barrier impairment
Summary
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. The inflammation associated with CD can affect any section and any tissue layer of the Macrophages play a major role in the body’s first line of defense against foreign antigens and control the barrier functions of the epithelial layers in the small intestine and colon [4]. Macrophages most often play a protective role against the development of acute colitis [5] Based on their state of activation, most macrophages can be grouped into two subtypes: classically activated and proinflammatory (M1) macrophages and alternatively activated and anti-inflammatory (M2) macrophages. The distinct functions of M1 macrophages and M2 macrophages in this context are not clear, and the various receptors, ligands and cytokines in the local microenvironment that govern intestinal barrier integrity have yet to be completely investigated
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