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...

Descripción completa

Detalles Bibliográficos
Autores principales: Prins, Marileen M., Verstockt, Bram, Ferrante, Marc, Vermeire, Séverine, Wildenberg, Manon E., Koelink, Pim J.
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