TREM-1–expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases
Mirjam Schenk, … , Frank Seibold, Christoph Mueller
Mirjam Schenk, … , Frank Seibold, Christoph Mueller
Published October 1, 2007
Citation Information: J Clin Invest. 2007;117(10):3097-3106. https://doi.org/10.1172/JCI30602.
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Research Article Inflammation

TREM-1–expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases

Abstract

Triggering receptor expressed on myeloid cells–1 (TREM-1) potently amplifies acute inflammatory responses by enhancing degranulation and secretion of proinflammatory mediators. Here we demonstrate that TREM-1 is also crucially involved in chronic inflammatory bowel diseases (IBD). Myeloid cells of the normal intestine generally lack TREM-1 expression. In experimental mouse models of colitis and in patients with IBD, however, TREM-1 expression in the intestine was upregulated and correlated with disease activity. TREM-1 significantly enhanced the secretion of relevant proinflammatory mediators in intestinal macrophages from IBD patients. Blocking TREM-1 by the administration of an antagonistic peptide substantially attenuated clinical course and histopathological alterations in experimental mouse models of colitis. This effect was also seen when the antagonistic peptide was administered only after the first appearance of clinical signs of colitis. Hence, TREM-1–mediated amplification of inflammation contributes not only to the exacerbation of acute inflammatory disorders but also to the perpetuation of chronic inflammatory disorders. Furthermore, interfering with TREM-1 engagement leads to the simultaneous reduction of production and secretion of a variety of pro-inflammatory mediators such as TNF, IL-6, IL-8 (CXCL8), MCP-1 (CCL2), and IL-1β. Therefore, TREM-1 may also represent an attractive target for the treatment of chronic inflammatory disorders.

Authors

Mirjam Schenk, Axel Bouchon, Frank Seibold, Christoph Mueller

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Figure 1

TREM-1–expressing macrophages are increased in the intestinal lamina propria of IBD patients.

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TREM-1–expressing macrophages are increased in the intestinal lamina pro...
(A) Serial frozen sections of the intestine from normal donors and IBD (CD and UC) patients with active disease were immunostained for TREM-1 and CD68. An isotype-matched irrelevant mAb was used as a negative control (Isotype ctrl). Stainings are representative of at least 12 different intestinal tissue samples for the normal small and large intestine and of at least 10 tissues each for UC and CD. Original magnification, ×40. (B) Double immunofluorescence stainings demonstrate that most TREM-1–positive cells (green) in the intestinal lamina propria from patients with active IBD (UC and CD) were CD68+ macrophages (red). Original magnification, ×100.