Therapeutic effect of leflunomide on the development of experimental lupus nephritis in mice.
Mice with chronic graft-versus-host disease (cGVHD) induced by transferring parental BALB/C lymphocytes into (C57BL/6 × BALB/C) F1 (CBF1) hybrids, develop a syndrome characterized by B-cell hyperactivity, autoantibody production, and immune complex-mediated glomerulonephritis. In this model, we evaluated the role of leflunomide on the development of lupus nephritis in system autoimmunity. Daily administration of leflunomide (15 mg/kg/d) from 2 weeks after cGVHD induction can dramatically reduce the production of autoantibodies and immune complex deposition in the kidney, leading to relieved kidney damage and reduced mortality. The therapeutic effect of leflunomide on the lupus-prone mice was partially due to the inhibition of TLR9 signaling pathway, which was an important component of innate immune system.
Department of Immunology, Norman Bethune Medical College, Jilin University, Changchun 130021, China.
Chunyan
C
He
Xuehong
X
Lu
Zhaowei
Z
Yan
Man
M
Wu
Shujun
S
Liu
Yongli
Y
Yu
Ping
P
Luo
D000818:Animals; D000936:Antigen-Antibody Complex / Q000187:drug effects / Q000276:immunology; D001201:Ascites / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007555:Isoxazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D000077339:Leflunomide; D008136:Longevity / Q000187:drug effects; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000378:metabolism
D000936:Antigen-Antibody Complex; D007166:Immunosuppressive Agents; D007555:Isoxazoles; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D000077339:Leflunomide