title: Interleukin-17 expression positively correlates with disease severity of lupus nephritis by increasing anti-double-stranded DNA antibody production in a lupus model induced by activated lymphocyte derived DNA.
abstract: Lupus nephritis is one of the most serious manifestations and one of the strongest predictors of a poor outcome in systemic lupus erythematosus (SLE). Recent evidence implicated a potential role of interlukin-17 (IL-17) in the pathogenesis of lupus nephritis. However, the correlation between IL-17 expression level and the severity of lupus nephritis still remains incompletely understood. In this study, we found that serum IL-17 expression level was associated with the severity of lupus nephritis, which was evaluated by histopathology of kidney sections and urine protein. Of note, we showed that enforced expression of IL-17 using adenovirus construct that expresses IL-17 could enhance the severity of lupus nephritis, while blockade of IL-17 using neutralizing antibody resulted in decreased severity of lupus nephritis. Consistently, we observed an impaired induction of lupus nephritis in IL-17-deficient mice. Further, we revealed that IL-17 expression level was associated with immune complex deposition and complement activation in kidney. Of interest, we found that IL-17 was crucial for increasing anti-double-stranded DNA (dsDNA) antibody production in SLE. Our results suggested that IL-17 expression level positively correlated with the severity of lupus nephritis, at least in part, because of its contribution to anti-dsDNA antibody production. These findings provided a novel mechanism for how IL-17 expression level correlated with disease pathogenesis and suggested that management of IL-17 expression level was a potential and promising approach for treatment of lupus nephritis.
authors.affiliation: Institute for Immunobiology, Shanghai Medical College of Fudan University, Shanghai, China.
authors.forename: Zhenke
authors.initials: Z
authors.lastname: Wen
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Gao
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D003167:Complement Activation; D004247:DNA; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D020381:Interleukin-17 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008181:Lupus Nephritis / Q000378:metabolism* / Q000652:urine; D008214:Lymphocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011507:Proteinuria / Q000473:pathology
chemical_list: D000974:Antibodies, Antinuclear; D020381:Interleukin-17; D004247:DNA