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| Status |
Public on Apr 07, 2021 |
| Title |
Expression profiles of TREM-1 high and TREM-1 low expressing monocytes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The expression of Triggering Receptor Expressed on Myeloid cells (TREM)-1 has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of TREM-1 specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment TREM-1 expression levels of CD14+ monocytes of Crohn’s disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low TREM-1 expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with TREM-1 expression levels in the CD patient cohort. In conclusion, our results indicate that TREM-1 expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of TREM-1.
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| Overall design |
Monocytes were isolated from healthy blood donor buffy coats (n=13). Cells were stained for expression of TREM-1, and sorted by flow cytometry into separate TREM-1 high (upper 30% of expressio range) and TREM-1 low (lowest 30% of expression range) populations.
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| Contributor(s) |
Koelink PJ, Wildenberg ME |
| Citation(s) |
33790898 |
| Submission date |
Jan 26, 2021 |
| Last update date |
Apr 07, 2021 |
| Contact name |
Manon Wildenberg |
| E-mail(s) |
m.e.wildenberg@amc.nl
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| Organization name |
Amsterdam UMC
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| Department |
Gastroenterology
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| Street address |
Meibergdreef 9
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| City |
Amsterdam |
| ZIP/Postal code |
1105AZ |
| Country |
Netherlands |
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| Platforms (1) |
| GPL23159 |
[Clariom_S_Human] Affymetrix Clariom S Assay, Human (Includes Pico Assay) |
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| Samples (26)
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| Relations |
| BioProject |
PRJNA694863 |
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