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Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy

Thomas D Barbour1, Guang Sheng Ling1, Marieta M Ruseva1

  • 1Centre for Complement and Inflammation Research, Imperial College, London, UK.

Kidney International
|March 1, 2016
PubMed

Insights

Complement receptor 3 (CR3) deficiency worsens C3 glomerulopathy in mice lacking factor H. CR3 protects against kidney injury by regulating macrophage inflammatory responses, suggesting therapeutic potential.

Area of Science:

  • Nephrology
  • Immunology
  • Complement System Biology

Background:

  • C3 glomerulopathy is a kidney disease driven by complement alternative pathway dysregulation.
  • Factor H deficiency (Cfh(-/-)) is a model for C3 glomerulopathy, characterized by C3 fragment deposition.
  • Complement receptor 3 (CR3) binds to C3 fragments like iC3b.

Purpose of the Study:

  • To investigate the role of CR3 in C3 glomerulopathy and other forms of nephritis.
  • To determine if CR3 deficiency exacerbates C3 glomerulopathy in Cfh(-/-) mice.
  • To explore the mechanism by which CR3 influences renal inflammation.

Main Methods:

  • Utilized Cfh(-/-) mice and CR3-deficient mice models.
  • Assessed renal disease severity and injury in different genetic backgrounds.
  • Examined the effect of iC3b-CR3 interaction on macrophage cytokine production in vitro.

Main Results:

  • CR3 deficiency significantly worsened spontaneous renal disease in Cfh(-/-) mice, dependent on bone marrow-derived cells.
  • CR3 deficiency led to enhanced renal injury in a model of accelerated nephrotoxic nephritis.
  • The interaction between iC3b and CR3 suppressed pro-inflammatory cytokine release from macrophages.

Conclusions:

  • CR3 plays a protective role in experimental glomerulonephritis and nephritis.
  • CR3 mitigates kidney injury by modulating macrophage-derived inflammatory cytokines.
  • Enhancing CR3-iC3b interactions may offer a therapeutic strategy for C3 glomerulopathy and related kidney diseases.

Keywords:
complementglomerulonephritismacrophages

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