Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin-GPR37 signaling

Purbasha Bhattacharya; Umesh Kumar Dhawan; Mohammed Tayab Hussain; Praveen Singh; Karran Kiran Bhagat; Aarushi Singhal; Shani Austin-Williams; Shantanu Sengupta; Manikandan Subramanian

Cell Reports (Jul 2023)

Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin-GPR37 signaling

Purbasha Bhattacharya,
Umesh Kumar Dhawan,
Mohammed Tayab Hussain,
Praveen Singh,
Karran Kiran Bhagat,
Aarushi Singhal,
Shani Austin-Williams,
Shantanu Sengupta,
Manikandan Subramanian

Affiliations

Purbasha Bhattacharya: CSIR – Institute of Genomics and Integrative Biology, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
Umesh Kumar Dhawan: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
Mohammed Tayab Hussain: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
Praveen Singh: CSIR – Institute of Genomics and Integrative Biology, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
Karran Kiran Bhagat: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
Aarushi Singhal: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
Shani Austin-Williams: William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
Shantanu Sengupta: CSIR – Institute of Genomics and Integrative Biology, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
Manikandan Subramanian: Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK; Corresponding author

Journal volume & issue: Vol. 42, no. 7
p. 112808

Abstract

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Summary: Macrophages release soluble mediators following efferocytic clearance of apoptotic cells to facilitate intercellular communication and promote the resolution of inflammation. However, whether inflammation resolution is modulated by extracellular vesicles (EVs) and vesicular mediators released by efferocytes is not known. We report that efferocyte-derived EVs express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor Tim4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation. Neutralization and knockdown of prosaposin or blocking GRP37 abrogates the pro-resolution effects of efferocyte-derived EVs in vivo. Administration of efferocyte-derived EVs in a murine model of atherosclerosis is associated with an increase in lesional macrophage efferocytosis efficiency and a decrease in plaque necrosis and lesional inflammation. Thus, we establish a critical role for efferocyte-derived vesicular mediators in increasing macrophage efferocytosis efficiency and accelerating the resolution of inflammation and tissue injury.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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