Cargando…
Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways
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 spe...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005579/ https://www.ncbi.nlm.nih.gov/pubmed/33790898 http://dx.doi.org/10.3389/fimmu.2021.627535 |
_version_ | 1783672138297769984 |
---|---|
author | Prins, Marileen M. Verstockt, Bram Ferrante, Marc Vermeire, Séverine Wildenberg, Manon E. Koelink, Pim J. |
author_facet | Prins, Marileen M. Verstockt, Bram Ferrante, Marc Vermeire, Séverine Wildenberg, Manon E. Koelink, Pim J. |
author_sort | Prins, Marileen M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8005579 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80055792021-03-30 Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways Prins, Marileen M. Verstockt, Bram Ferrante, Marc Vermeire, Séverine Wildenberg, Manon E. Koelink, Pim J. Front Immunol Immunology 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. Frontiers Media S.A. 2021-03-15 /pmc/articles/PMC8005579/ /pubmed/33790898 http://dx.doi.org/10.3389/fimmu.2021.627535 Text en Copyright © 2021 Prins, Verstockt, Ferrante, Vermeire, Wildenberg and Koelink http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Prins, Marileen M. Verstockt, Bram Ferrante, Marc Vermeire, Séverine Wildenberg, Manon E. Koelink, Pim J. Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways |
title | Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways |
title_full | Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways |
title_fullStr | Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways |
title_full_unstemmed | Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways |
title_short | Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways |
title_sort | monocyte trem-1 levels associate with anti-tnf responsiveness in ibd through autophagy and fcγ-receptor signaling pathways |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005579/ https://www.ncbi.nlm.nih.gov/pubmed/33790898 http://dx.doi.org/10.3389/fimmu.2021.627535 |
work_keys_str_mv | AT prinsmarileenm monocytetrem1levelsassociatewithantitnfresponsivenessinibdthroughautophagyandfcgreceptorsignalingpathways AT verstocktbram monocytetrem1levelsassociatewithantitnfresponsivenessinibdthroughautophagyandfcgreceptorsignalingpathways AT ferrantemarc monocytetrem1levelsassociatewithantitnfresponsivenessinibdthroughautophagyandfcgreceptorsignalingpathways AT vermeireseverine monocytetrem1levelsassociatewithantitnfresponsivenessinibdthroughautophagyandfcgreceptorsignalingpathways AT wildenbergmanone monocytetrem1levelsassociatewithantitnfresponsivenessinibdthroughautophagyandfcgreceptorsignalingpathways AT koelinkpimj monocytetrem1levelsassociatewithantitnfresponsivenessinibdthroughautophagyandfcgreceptorsignalingpathways |