A defect in Marco expression contributes to systemic lupus erythematosus development via failure to clear apoptotic cells.
Systemic lupus erythematosus is a multisystem autoimmune disease characterized by the production of numerous antinuclear autoantibodies and inflammatory mediators. The BXSB mouse strain is an excellent model of the disease. Previous work has determined a number of important disease susceptibility intervals that have been isolated in separate congenic strains. Here, we have combined expression data from those strains with functional analyses to demonstrate that reduced expression of the innate scavenger receptor Marco (macrophage receptor with collagenous structure) is a primary event in BXSB mice, that reduced mRNA expression is mirrored at the protein level, and that this results in a significant alteration in function. We have confirmed a role for Marco in the clearance of apoptotic cells and a generalized defect in both endocytosis and phagocytosis. The failure to clear apoptotic cells has previously been linked to the development of systemic lupus erythematosus. However, the use of congenic mice with limited phenotypes in this study has enabled us to propose that in the case of Marco at least, disease results from the production of anti-dsDNA Abs.
Rogers
Nicola Jane
NJ
Immunology Department, Faculty of Medicine, Imperial College London, Hammersmith Campus, London, UK. nicola.rogers@imperial.ac.uk
Lees
Mark Jeffrey
MJ
Gabriel
Luisa
L
Maniati
Eleni
E
Rose
Sarah Jane
SJ
Potter
Paul Keith
PK
Morley
Bernard John
BJ
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D004705:Endocytosis / Q000502:physiology; D005434:Flow Cytometry; D015870:Gene Expression; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051379:Mice; D020297:Mice, Congenic; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000974:Antibodies, Antinuclear; C092228:Marco protein, mouse; D011971:Receptors, Immunologic