IL-35 Decelerates the Inflammatory Process by Regulating Inflammatory Cytokine Secretion and M1/M2 Macrophage Ratio in Psoriasis

• Published in: The Journal of immunology (1950) Vol. 197; no. 6; pp. 2131 - 2144
• Main Authors: Zhang, Junfeng, Lin, Yi, Li, Chunlei, Zhang, Xiaomei, Cheng, Lin, Dai, Lei, Wang, Youcui, Wang, Fangfang, Shi, Gang, Li, Yiming, Yang, Qianmei, Cui, Xueliang, Liu, Yi, Wang, Huiling, Zhang, Shuang, Yang, Yang, Xiang, Rong, Li, Jiong, Yu, Dechao, Wei, Yuquan, Deng, Hongxin
• Format: Journal Article
• Language: English
• Published: United States 15.09.2016
• Subjects: Animals; Cells, Cultured; Cytokines - biosynthesis; Dexamethasone - pharmacology; Humans; Inflammation - drug therapy; Inflammation - immunology; Interleukin-6 - biosynthesis; Interleukin-8 - biosynthesis; Interleukins - pharmacology; Interleukins - therapeutic use; Keratinocytes - metabolism; Macrophages - drug effects; Macrophages - physiology; Mice; Mice, Inbred BALB C; Psoriasis - drug therapy; Psoriasis - immunology; S100 Calcium Binding Protein A7; S100 Proteins - biosynthesis; Th17 Cells - drug effects; Th17 Cells - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1600446

IL-35 downregulates Th17 cell development and suppresses certain types of autoimmune inflammation such as collagen-induced arthritis and experimental autoimmune uveitis. Psoriasis is thought to be initiated by abnormal interactions between cutaneous keratinocytes and systemic immune cells. However, the role of IL-35 in psoriasis remains unclear. In this study, we assessed IL-35 in three well-known psoriasis models: a human keratinocyte cell line (HaCaT), a keratin 14 (K14)-vascular endothelial growth factor A (VEGF-A)-transgenic (Tg) mouse model, and an imiquimod-induced psoriasis mouse model. First, we found that IL-35 suppressed the expression of IL-6, CXCL8, and S100A7, which are highly upregulated by a mixture of five proinflammatory cytokines in HaCaT. Second, a plasmid coding for the human IL-35 sequence coated with cationic liposomes showed potent immunosuppressive effects on K14-VEGF-A-Tg and imiquimod-induced psoriasis mouse models. In the K14-VEGF-A-Tg model, our results showed that several types of proinflammatory cytokines were significantly reduced, whereas IL-10 was remarkably induced by IL-35. Compared with pcDNA3.1, there was a small number of CD4(+)IL-17(+) T cells and a large number of CD4(+)IL-10(+) and CD4(+)CD25(+)Foxp3(+) T cells in the IL-35 group. Most importantly, we found that IL-35 decreased the total number of macrophages and ratio of M1/M2 macrophages, which has not been reported previously. In addition, compared with dexamethasone, IL-35 showed long-term therapeutic efficacy. In summary, our results strongly indicate that IL-35 plays a potent immunosuppressive role in psoriasis. Thus, IL-35 has potential for development as a new therapeutic strategy for patients with chronic psoriasis and other cutaneous inflammatory diseases.