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Updated: Aug 23, 2025

Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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GPR97 triggers inflammatory processes in human neutrophils via a macromolecular complex upstream of PAR2 activation

Tai-Ying Chu1, Céline Zheng-Gérard2, Kuan-Yeh Huang1

  • 1Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Nature Communications
|October 27, 2022
PubMed

Insights

Researchers discovered a protein complex that activates neutrophils, driving inflammation and anti-microbial responses. This complex, involving GPR97 and membrane proteinase 3 (mPR3), offers a potential therapeutic target for inflammatory diseases.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Neutrophils are crucial for host defense against microbes but require strict regulation to prevent inflammatory and autoimmune diseases.
  • Dysfunctional neutrophil activity is implicated in various pathological conditions.

Purpose of the Study:

  • To elucidate the mechanism by which the adhesion molecule GPR97 activates neutrophils.
  • To identify the protein complex involved in neutrophil activation and its role in inflammation.

Main Methods:

  • Crystallographic and deletion analysis of the GPR97 extracellular region.
  • Investigation of protein-protein interactions within the CD177/GPR97/PAR2/CD16b complex.
  • Assessment of PAR2 activation and downstream inflammatory signaling.

Main Results:

  • GPR97 allosterically activates membrane proteinase 3 (mPR3), leading to neutrophil activation.
  • The CD177/GPR97/PAR2/CD16b complex is essential for mPR3 activation and subsequent PAR2 signaling.
  • PAR2 activation by this complex triggers strong inflammatory responses, including anti-microbial activities and endothelial dysfunction.
  • Upregulation of GPR97 and mPR3 on disease-associated neutrophils highlights their role in pathological inflammation.

Conclusions:

  • A novel mechanism for PAR2 activation has been identified, regulating neutrophil activation and inflammation.
  • The identified protein complex (PR3/CD177/GPR97/PAR2/CD16b) is a key mediator of neutrophil-driven inflammation.
  • This complex represents a promising therapeutic target for managing neutrophil-mediated inflammatory diseases.

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