Loss of LFA-1, but not Mac-1, protects MRL/MpJ-Fas(lpr) mice from autoimmune disease.
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 beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) 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.
Kevil
Christopher G
CG
Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
Hicks
M John
MJ
He
Xiaodong
X
Zhang
Junxuan
J
Ballantyne
Christie M
CM
Raman
Chander
C
Schoeb
Trenton R
TR
Bullard
Daniel C
DC
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D018845:CD11 Antigens / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D005921:Glomerulonephritis / Q000517:prevention & control*; D007677:Kidney Function Tests; D008180:Lupus Erythematosus, Systemic / Q000473:pathology / Q000517:prevention & control*; D008206:Lymphatic Diseases / Q000517:prevention & control*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout
D001323:Autoantibodies; D018845:CD11 Antigens; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen