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

• Published in: Clinical rheumatology 2014-11, Vol.33 (11), p.1585-1593
• Main Authors: Mao, Xiaoli, Wu, Yunyun, Diao, Huitian, Hao, Jianlei, Tian, Gaofei, Jia, Zhenghu, Li, Zheng, Xiong, Sidong, Wu, Zhenzhou, Wang, Puyue, Zhao, Liqing, Yin, Zhinan
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Antinuclear - immunology; Disease Models, Animal; Disease Progression; DNA - immunology; Female; Forkhead Transcription Factors - metabolism; Interleukin-6 - metabolism; Kidney - pathology; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lupus Erythematosus, Systemic - pathology; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Knockout; Original Article; Rheumatology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-014-2717-9

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.