TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn's Disease Patients
© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation..
BACKGROUND AND AIMS: Uncontrolled activation of intestinal mononuclear phagocytes [MNPs] drives chronic inflammation in inflammatory bowel disease [IBD]. Triggering receptor expressed on myeloid cells 1 [TREM-1] has been implicated in the pathogenesis of IBD. However, the role of TREM-1+ cell subsets in driving IBD pathology and the link with clinical parameters are not understood. We investigated TREM-1 expression in human intestinal MNP subsets and examined blocking TREM-1 as a potential IBD therapy.
METHODS: TREM-1 gene expression was analysed in intestinal mucosa, enriched epithelial and lamina propria [LP] layers, and purified cells from controls and IBD patients. TREM-1 protein on immune cells was assessed by flow cytometry and immunofluorescence microscopy. Blood monocyte activation was examined by large-scale gene expression using a TREM-1 agonist or LP conditioned media [LP-CM] from patients in the presence or absence of TREM-1 and tumour necrosis factor [TNF] antagonist antibodies.
RESULTS: TREM-1 gene expression increases in intestinal mucosa from IBD patients and correlates with disease score. TREM-1+ cells, which are mainly immature macrophages and CD11b+ granulocytes, increase among LP cells from Crohn's disease patients and their frequency correlates with inflammatory molecules in LP-CM. LP-CM from Crohn's disease patients induces an inflammatory transcriptome in blood monocytes, including increased IL-6 expression, which is reduced by simultaneous blocking of TREM-1 and TNF.
CONCLUSIONS: High intestinal TREM-1 expression, reflecting a high frequency of TREM-1+ immature macrophages and TREM-1+CD11b+ granulocytes, is linked to the deleterious inflammatory microenvironment in IBD patients. Therefore, blocking the TREM-1 pathway, especially simultaneously with anti-TNF therapy, has potential as a new IBD therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Journal of Crohn's & colitis - 15(2021), 8 vom: 02. Aug., Seite 1346-1361 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Caër, Charles [VerfasserIn] |
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| Links: |
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| Themen: |
CD11b Antigen |
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| Anmerkungen: |
Date Completed 15.12.2021 Date Revised 15.12.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/ecco-jcc/jjab022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM320984877 |
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| 245 | 1 | 0 | |a TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn's Disease Patients |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. | ||
| 520 | |a BACKGROUND AND AIMS: Uncontrolled activation of intestinal mononuclear phagocytes [MNPs] drives chronic inflammation in inflammatory bowel disease [IBD]. Triggering receptor expressed on myeloid cells 1 [TREM-1] has been implicated in the pathogenesis of IBD. However, the role of TREM-1+ cell subsets in driving IBD pathology and the link with clinical parameters are not understood. We investigated TREM-1 expression in human intestinal MNP subsets and examined blocking TREM-1 as a potential IBD therapy | ||
| 520 | |a METHODS: TREM-1 gene expression was analysed in intestinal mucosa, enriched epithelial and lamina propria [LP] layers, and purified cells from controls and IBD patients. TREM-1 protein on immune cells was assessed by flow cytometry and immunofluorescence microscopy. Blood monocyte activation was examined by large-scale gene expression using a TREM-1 agonist or LP conditioned media [LP-CM] from patients in the presence or absence of TREM-1 and tumour necrosis factor [TNF] antagonist antibodies | ||
| 520 | |a RESULTS: TREM-1 gene expression increases in intestinal mucosa from IBD patients and correlates with disease score. TREM-1+ cells, which are mainly immature macrophages and CD11b+ granulocytes, increase among LP cells from Crohn's disease patients and their frequency correlates with inflammatory molecules in LP-CM. LP-CM from Crohn's disease patients induces an inflammatory transcriptome in blood monocytes, including increased IL-6 expression, which is reduced by simultaneous blocking of TREM-1 and TNF | ||
| 520 | |a CONCLUSIONS: High intestinal TREM-1 expression, reflecting a high frequency of TREM-1+ immature macrophages and TREM-1+CD11b+ granulocytes, is linked to the deleterious inflammatory microenvironment in IBD patients. Therefore, blocking the TREM-1 pathway, especially simultaneously with anti-TNF therapy, has potential as a new IBD therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Crohn’s disease | |
| 650 | 4 | |a IL-6 | |
| 650 | 4 | |a TNF | |
| 650 | 4 | |a TREM-1 | |
| 650 | 4 | |a intestinal inflammation | |
| 650 | 4 | |a macrophages | |
| 650 | 7 | |a CD11b Antigen |2 NLM | |
| 650 | 7 | |a ITGAM protein, human |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Triggering Receptor Expressed on Myeloid Cells-1 |2 NLM | |
| 700 | 1 | |a Gorreja, Frida |e verfasserin |4 aut | |
| 700 | 1 | |a Forsskåhl, Sophia K |e verfasserin |4 aut | |
| 700 | 1 | |a Brynjolfsson, Siggeir F |e verfasserin |4 aut | |
| 700 | 1 | |a Szeponik, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Magnusson, Maria K |e verfasserin |4 aut | |
| 700 | 1 | |a Börjesson, Lars G |e verfasserin |4 aut | |
| 700 | 1 | |a Block, Mattias |e verfasserin |4 aut | |
| 700 | 1 | |a Bexe-Lindskog, Elinor |e verfasserin |4 aut | |
| 700 | 1 | |a Wick, Mary Jo |e verfasserin |4 aut | |
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