PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function

Mariaelvy Bianchini, Johan Duchene*, Donato Santovito, Maximilian J. Schloss, Maximilien Evrard, Holger Winkels, Maria Aslani, Sarajo K. Mohanta, Michael Horckmans, Xavier Blanchet, Michael Lacy, Philipp von Hundelshausen, Dorothee Atzler, Andreas Habenicht, Norbert Gerdes, Jaroslav Pelisek, Lai Guan Ng, Sabine Steffens, Christian Weber*, Remco T. A. Megens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Web of Science)

Abstract

The role of nonclassical monocytes (NCMs) in health and disease is emerging, but their location and function within tissues remain poorly explored. Imaging of NCMs has been limited by the lack of an established single NCM marker. Here, we characterize the immune checkpoint molecule PD-L1 (CD274) as an unequivocal marker for tracking NCMs in circulation and pinpoint their compartmentalized distribution in tissues by two-photon microscopy. Visualization of PD-L1(+) NCMs in relation to bone marrow vasculature reveals that conversion of classical monocytes into NCMs requires contact with endosteal vessels. Furthermore, PD-L1(+) NCMs are present in tertiary lymphoid organs (TLOs) under inflammatory conditions in both mice and humans, and NCMs exhibit a PD-L1-dependent immunomodulatory function that promotes T cell apoptosis within TLOs. Our findings establish an unambiguous tool for the investigation of NCMs and shed light on their origin and function.

Original languageEnglish
Article number3054
Number of pages14
JournalScience Immunology
Volume4
Issue number36
DOIs
Publication statusPublished - Jun 2019

Keywords

  • BLOOD-VESSELS
  • CELLS
  • MACROPHAGES
  • CX(3)CR1
  • MOUSE

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