title: Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model.
abstract: Our aim is to reveal the role of interleukin 6 (IL-6) in the pathogenesis of systemic lupus erythematosus (SLE) in a murine model of SLE. Normal female C57BL/6 mice were immunized with syngeneic-activated lymphocyte-derived DNA (ALD-DNA) to induce SLE. Non-immunized mice were used as control. SLE-associated markers, including anti-double-stranded DNA (anti-dsDNA) Abs, urine protein, and kidney histopathology, were assayed to ensure the induction of the disease. Compared with control mice, ALD-DNA immunized mice exhibited high levels of anti-dsDNA Abs, IL-6 expression in vivo and in vitro. We also found that IL-6 knockout (IL-6KO) mice were resistant to ALD-DNA-induced SLE. The activation of CD4(+) T cells in immunized IL-6KO mice was lower than in immunized wild-type (Wt) mice. Intracellular cytokine staining showed that Foxp3 expression in immunized IL-6KO mice was higher than in immunized Wt mice, which might be associated with the disease severity. We further discovered that ALD-DNA-stimulated dendritic cells supernatants could result in higher IL-6 and TNF-α expression and could suppress Foxp3 expression. In addition, blocking IL-6 could up-regulate Foxp3 expression. Therefore, our findings show that IL-6 promotes the progression of SLE via suppressing Treg differentiation.
authors.affiliation: Department of Immunology, School of Basic Medical Science, Wuhan University, Wuhan, 430200, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Mao
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Wu
authors.forename: Huitian
authors.initials: H
authors.lastname: Diao
authors.forename: Jianlei
authors.initials: J
authors.lastname: Hao
authors.forename: Gaofei
authors.initials: G
authors.lastname: Tian
authors.forename: Zhenghu
authors.initials: Z
authors.lastname: Jia
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Puyue
authors.initials: P
authors.lastname: Wang
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhinan
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007668:Kidney / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000974:Antibodies, Antinuclear; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004247:DNA