p53 is required for spontaneous autoantibody production in B6/lpr lupus mice.
The p53 tumor suppressor molecule triggers a key pathway of apoptosis in injured cells, in part through induction of Fas. The importance of Fas as a receptor mediating apoptosis is highlighted by the lupus-like systemic autoimmunity seen in animals and humans with nonfunctional Fas molecules. We set out to see if the absence of p53, superimposed on the Fas defect of lpr mice, might further accelerate or exacerbate their systemic autoimmunity. We generated double mutant mice (p53(-/-) lpr) having defects in both p53- and Fas-dependent pathways, hypothesizing that animals with lesions in both Fas- and p53-dependent pathways would show reduced ability to delete autoreactive or injured cells, thereby producing more severe autoimmune disease. Surprisingly, these mice have lower autoantibody levels than the single mutant lpr mice. These studies suggest an unanticipated role for p53 in the progression of autoimmunity and the production of autoantibodies.
Kuan
Anita P
AP
Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, USA.
Cohen
Philip L
PL
D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D012867:Skin / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000276:immunology; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor