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(American Journal of Pathology. 2004;165:609-616.)
© 2004 American Society for Investigative Pathology

Loss of LFA-1, but not Mac-1, Protects MRL/MpJ-Fas^lpr Mice from Autoimmune Disease

Christopher G. Kevil^*, M. John Hicks, Xiaodong He, Junxuan Zhang, Christie M. Ballantyne, Chander Raman^¶, Trenton R. Schoeb and Daniel C. Bullard

From the Department of Pathology,^* Louisiana State University Health Sciences Center, Shreveport, Louisiana; the Departments of Pathology and Medicine, Baylor College of Medicine, Houston Texas; and the Departments of Genetics and Medicine,^¶ University of Alabama at Birmingham, Birmingham, Alabama

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas^lpr mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in ß₂ integrin-deficient (CD18-null) MRL/MpJ-Fas^lpr mice, suggesting a lack of redundancy among the ß₂ integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE.

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