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

doi:10.1126/sciimmunol.aar3054

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 journal › Article › Academic › peer-review

34 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 language	English
Article number	3054
Number of pages	14
Journal	Science Immunology
Volume	4
Issue number	36
DOIs	https://doi.org/10.1126/sciimmunol.aar3054
Publication status	Published - Jun 2019

Keywords

BLOOD-VESSELS
CELLS
MACROPHAGES
CX(3)CR1
MOUSE

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10.1126/sciimmunol.aar3054

Cite this

Bianchini, M., Duchene, J., Santovito, D., Schloss, M. J., Evrard, M., Winkels, H., Aslani, M., Mohanta, S. K., Horckmans, M., Blanchet, X., Lacy, M., von Hundelshausen, P., Atzler, D., Habenicht, A., Gerdes, N., Pelisek, J., Ng, L. G., Steffens, S., Weber, C., & Megens, R. T. A. (2019). PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function. Science Immunology, 4(36), Article 3054. https://doi.org/10.1126/sciimmunol.aar3054

@article{cfb04b03b5f940be8875ca2c97b4906e,

title = "PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function",

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.",

keywords = "BLOOD-VESSELS, CELLS, MACROPHAGES, CX(3)CR1, MOUSE",

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

note = "Funding Information: Funding: The present work was supported by the Deutsche Forschungsgemeinschaft grants Publisher Copyright: Copyright {\textcopyright} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works",

year = "2019",

month = jun,

doi = "10.1126/sciimmunol.aar3054",

language = "English",

volume = "4",

journal = "Science Immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

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Bianchini, M, Duchene, J, Santovito, D, Schloss, MJ, Evrard, M, Winkels, H, Aslani, M, Mohanta, SK, Horckmans, M, Blanchet, X, Lacy, M, von Hundelshausen, P, Atzler, D, Habenicht, A, Gerdes, N, Pelisek, J, Ng, LG, Steffens, S, Weber, C & Megens, RTA 2019, 'PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function', Science Immunology, vol. 4, no. 36, 3054. https://doi.org/10.1126/sciimmunol.aar3054

TY - JOUR

T1 - PD-L1 expression on nonclassical monocytes reveals their origin and immunoregulatory function

AU - Bianchini, Mariaelvy

AU - Duchene, Johan

AU - Santovito, Donato

AU - Schloss, Maximilian J.

AU - Evrard, Maximilien

AU - Winkels, Holger

AU - Aslani, Maria

AU - Mohanta, Sarajo K.

AU - Horckmans, Michael

AU - Blanchet, Xavier

AU - Lacy, Michael

AU - von Hundelshausen, Philipp

AU - Atzler, Dorothee

AU - Habenicht, Andreas

AU - Gerdes, Norbert

AU - Pelisek, Jaroslav

AU - Ng, Lai Guan

AU - Steffens, Sabine

AU - Weber, Christian

AU - Megens, Remco T. A.

N1 - Funding Information: Funding: The present work was supported by the Deutsche Forschungsgemeinschaft grants Publisher Copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

PY - 2019/6

Y1 - 2019/6

N2 - 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.

AB - 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.

KW - BLOOD-VESSELS

KW - CELLS

KW - MACROPHAGES

KW - CX(3)CR1

KW - MOUSE

U2 - 10.1126/sciimmunol.aar3054

DO - 10.1126/sciimmunol.aar3054

M3 - Article

C2 - 31227596

SN - 2470-9468

VL - 4

JO - Science Immunology

JF - Science Immunology

IS - 36

M1 - 3054

ER -