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Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen

Tracy L McGaha1, Yunying Chen, Buvana Ravishankar

  • 1Department of Medicine, Immunotherapy Center, Georgia Health Sciences University, 1120 15th Street, Augusta, GA 30912, USA. tmcgaha@georgiahealth.edu

Blood
|March 30, 2011
PubMed

Insights

Marginal zone macrophages (MZMs) are crucial for preventing immune responses to cellular debris. Depleting MZMs in mice led to increased autoimmune disease and mortality, highlighting their role in immune tolerance.

Area of Science:

  • Immunology
  • Cell Biology
  • Pathology

Background:

  • Marginal zone macrophages (MZMs) are specialized splenic macrophages involved in processing circulating materials.
  • Their role in regulating immune responses to apoptotic cells is not fully understood.

Purpose of the Study:

  • To investigate the function of MZMs in immunity to systemically administered apoptotic cells.
  • To determine if MZMs regulate the immunogenicity of autoantigens.

Main Methods:

  • Marginal zone macrophages (MZMs) were depleted in mice.
  • Innate and adaptive immune responses to systemically administered apoptotic cells were assessed.
  • Autoimmune disease progression and mortality were evaluated.

Main Results:

  • MZM depletion caused apoptotic cells to accumulate in T-cell areas.
  • Phagocytosis by other macrophages increased, with elevated expression of CD86, MHCII, and CCR7.
  • Proinflammatory cytokine production and lymphocyte responsiveness to apoptotic antigens were enhanced.
  • Autoimmune disease accelerated in lupus-prone mice and mortality increased in wild-type mice.

Conclusions:

  • Marginal zone macrophages (MZMs) play a critical role in clearing apoptotic cells.
  • MZMs are essential for minimizing the immunogenicity of autoantigens and maintaining immune tolerance.
  • MZM dysfunction may contribute to autoimmune disease pathogenesis.

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