Immunomodulatory endothelial cells contribute to T-cell recruitment and activation via antigen presentation on MHC II
A subset of endothelial cells referred to as immunomodulatory endothelial cells (IMEC) has been proposed to regulate T-cell responses in atherosclerosis and after myocardial infarction. Here, we studied the inflammation-induced emergence of IMEC and characterized their crosstalk with T cells.An in v...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
29 June 2026
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| In: |
Cardiovascular research
Year: 2026, Pages: 1-17 |
| ISSN: | 1755-3245 |
| DOI: | 10.1093/cvr/cvag137 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/cvr/cvag137
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| Author Notes: | Matteo Cartura, Blerina Aliraj, Witold Szymański, Christian Park, Giulio Ferrario, Flávia Rezende, Beyza Güven, Tore Bleckwehl, Nadja Sachs, Lars Mägdefessel, Stefanie Dimmeler, Oliver J. Müller, Hanjoong Jo, Stefan Offermanns, Sikander Hayat, Ralf P. Brandes, Christian Münch, Johannes Graumann, Andreas Weigert, Ingrid Fleming, and Mauro Siragusa |
| Summary: | A subset of endothelial cells referred to as immunomodulatory endothelial cells (IMEC) has been proposed to regulate T-cell responses in atherosclerosis and after myocardial infarction. Here, we studied the inflammation-induced emergence of IMEC and characterized their crosstalk with T cells.An in vitro model to study IMEC was characterized using flow cytometry and proteomics. Endothelial cell-specific translatome and single-cell transcriptome data from a murine atherogenesis model and single-cell transcriptome data from human atherosclerotic arteries were used to determine pathophysiological relevance. Immunopeptidomics was performed to detect antigen presentation. T-cell chemotaxis, adhesion, and activation were assessed through flow cytometry and microscopy. IMEC were induced by treating human endothelial cells with interleukin-1β, interferon-γ, and transforming growth factor-β2 and expressed lower levels of classical endothelial cell markers and disrupted VE-cadherin expression accompanied by impaired barrier function. IMEC expressed major histocompatibility complex (MHC) class II, proteins involved in antigen processing and presentation (CD83, CD80, and CD86) and pro-inflammatory cytokines as well as chemokines, including CXCL9. An IMEC-like subpopulation was identified in the lumen of carotid arteries in a mouse model of accelerated atherogenesis as well as in human atheromas. Conditioned medium from IMEC enhanced the migration of peripheral blood mononuclear cells and induced T-cell chemotaxis, which was partially inhibited by antagonizing CXCL9. IMEC exhibited a significant down-regulation of proteins related to glycosaminoglycan degradation, consistent with the key role of the glycocalyx in the establishment of chemokine gradients. Indeed, the accumulation of heparan sulphates in IMEC contributed to the adhesion of T cells. Notably, IMEC that had been exposed to monocyte lysates presented 627 peptide antigens on MHC class II and induced T-cell expansion.Our data highlight the role of IMEC as non-professional antigen-presenting cells that potentially contribute to T cell-mediated immune responses in cardiovascular disease. |
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| Item Description: | Gesehen am 28.07.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1755-3245 |
| DOI: | 10.1093/cvr/cvag137 |