4.7 Article

Immunomodulation by endothelial cells - partnering up with the immune system?

Journal

NATURE REVIEWS IMMUNOLOGY
Volume 22, Issue 9, Pages 576-588

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41577-022-00694-4

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Funding

  1. Marie Skodowska-Curie individual fellowship
  2. Fonds Wetenschappelijk Onderzoek (FWO)
  3. long-term structural Methusalem - Flemish Government, FWO
  4. Foundation Against Cancer [2016-078]
  5. European Research Council (ERC) Advanced Research Grant [EU-ERC743074]
  6. ERC Proof of Concept grant [ERC-713758]
  7. VIB TechWatch
  8. Novo Nordisk Foundation [NNF19OC0055802]

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Blood vessel endothelial cells (ECs) play a crucial role in regulating inflammation, and specific subtypes of ECs in different tissues and organs have distinct immunomodulatory capacities. These specific subtypes could be considered as targets for new immunotherapeutic approaches.
Blood vessel endothelial cells (ECs) have long been known to modulate inflammation by regulating immune cell trafficking, activation status and function. However, whether the heterogeneous EC populations in various tissues and organs differ in their immunomodulatory capacity has received insufficient attention, certainly with regard to considering them for alternative immunotherapy. Recent single-cell studies have identified specific EC subtypes that express gene signatures indicative of phagocytosis or scavenging, antigen presentation and immune cell recruitment. Here we discuss emerging evidence suggesting a tissue-specific and vessel type-specific immunomodulatory role for distinct subtypes of ECs, here collectively referred to as 'immunomodulatory ECs' (IMECs). We propose that IMECs have more important functions in immunity than previously recognized, and suggest that these might be considered as targets for new immunotherapeutic approaches. In this Perspective, Amersfoort, Eelen and Carmeliet discuss emerging evidence for tissue- and vessel type-specific immunomodulatory roles of distinct subtypes of endothelial cells, which they collectively refer to as 'immunomodulatory endothelial cells' (IMECs).

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