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Published on: November 1, 2015
Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase
Philip L Cohen1, Roberto Caricchio, Valsamma Abraham
1Department of Medicine, Division of Rheumatology, University of Pennsylvania, and Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. philipco@mail.med.upenn.edu
Abstract:
Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macro-phage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer-deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity.
Insights
Mice lacking the c-mer tyrosine kinase show impaired clearance of apoptotic cells, leading to lupus-like autoimmunity. This discovery offers a new model for studying how cellular debris triggers autoimmune diseases.
Area of Science:
- Immunology
- Cell Biology
- Autoimmunity
Background:
- The c-mer tyrosine kinase (c-mer) plays a role in macrophage function.
- Defects in c-mer signaling are associated with altered cytokine production and phagocytosis of apoptotic cells.
Purpose of the Study:
- To investigate the in vivo role of c-mer in apoptotic cell clearance and autoimmunity.
- To establish a mouse model for studying the immunogenicity of apoptotic debris.
Main Methods:
- Generation and analysis of c-mer-deficient mice.
- Assessment of apoptotic cell clearance using infused labeled apoptotic cells.
- Serological analysis for autoantibodies (anti-chromatin, anti-DNA, anti-IgG).
- Evaluation of B cell activation.
Main Results:
- C-mer-deficient mice exhibit impaired clearance of infused apoptotic cells.
- These mice develop progressive lupus-like autoimmunity, characterized by autoantibodies.
- Autoimmunity is driven by endogenous antigens with minimal polyclonal B cell activation.
Conclusions:
- C-mer is crucial for effective clearance of apoptotic cells in vivo.
- Failure to clear apoptotic debris can trigger systemic autoimmunity.
- C-mer-deficient mice represent a valuable model for autoimmune disease research.
