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

Purbasha Bhattacharya1, Umesh Kumar Dhawan2, Mohammed Tayab Hussain2

  • 1CSIR - Institute of Genomics and Integrative Biology, New Delhi, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

Cell Reports
|July 12, 2023
PubMed

Insights

Efferocyte-derived extracellular vesicles (EVs) carrying prosaposin enhance macrophage efferocytosis and accelerate inflammation resolution. Blocking prosaposin or GPR37 hinders these beneficial effects, highlighting a novel mechanism in tissue repair.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Macrophages resolve inflammation via soluble mediators after clearing apoptotic cells.
  • The role of extracellular vesicles (EVs) from efferocytes in inflammation resolution remains unclear.

Purpose of the Study:

  • To investigate the role of efferocyte-derived EVs in modulating inflammation resolution.
  • To identify the specific mediators within these EVs and their mechanisms of action.

Main Methods:

  • Characterization of efferocyte-derived EVs for prosaposin expression.
  • Analysis of prosaposin-GPR37 interaction and downstream signaling (ERK-AP1).
  • Assessment of Tim4 expression and efferocytosis efficiency in macrophages.
  • In vivo studies using neutralization, knockdown, and GPR37 blocking in atherosclerosis models.

Main Results:

  • Efferocyte-derived EVs express prosaposin, which binds macrophage GPR37.
  • Prosaposin binding increases Tim4 expression via an ERK-AP1 pathway, enhancing efferocytosis.
  • Neutralization or knockdown of prosaposin, or GPR37 blockade, abrogates the pro-resolution effects.
  • EV administration in atherosclerosis models improved efferocytosis, reduced necrosis, and decreased inflammation.

Conclusions:

  • Efferocyte-derived EVs, via prosaposin, enhance macrophage efferocytosis and accelerate inflammation resolution.
  • This pathway is critical for tissue repair and reducing inflammatory injury.
  • Prosaposin-GPR37 signaling represents a novel therapeutic target for inflammatory diseases.

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