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Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model

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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.

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Acknowledgments

This work was supported by grants to Dr. Z. Yin from the National Science Foundation of China (31230025), the International S&T Cooperation Program of China (2010DFB3400), and the National Basic Research Grant of China (2010CB529100). It was also supported by grants from the National Science Foundation of China (31170858, 31370883 to Dr. L. Zhao, and 31000400 to Dr. Z. Wu). We thank Charron Cote for editing the manuscript.

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Authors and Affiliations

  1. Department of Immunology, School of Basic Medical Science, Wuhan University, Wuhan, 430200, China

    Xiaoli Mao

  2. State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China

    Yunyun Wu, Huitian Diao, Jianlei Hao, Gaofei Tian, Zhenghu Jia, Zheng Li, Zhenzhou Wu, Puyue Wang, Liqing Zhao & Zhinan Yin

  3. Institute for Immunobiology and Department of Immunology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Sidong Xiong

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  1. Xiaoli Mao
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Correspondence to Zhinan Yin.

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Mao, X., Wu, Y., Diao, H. et al. Interleukin-6 promotes systemic lupus erythematosus progression with Treg suppression approach in a murine systemic lupus erythematosus model. Clin Rheumatol 33, 1585–1593 (2014). https://doi.org/10.1007/s10067-014-2717-9

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  • DOI: https://doi.org/10.1007/s10067-014-2717-9

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