title: IL-35 Decelerates the Inflammatory Process by Regulating Inflammatory Cytokine Secretion and M1/M2 Macrophage Ratio in Psoriasis.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Provincial Key Discipline of Medical Immunology, Jining Medical University, Jining 272067, Shandong, China;
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Yi
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Biochemistry, Faculty of Basic Medicine, Chongqing Three Gorges Medical College, Chongqing 400715, China;
authors.forename: Chunlei
authors.initials: C
authors.lastname: Li
authors.affiliation: Laboratory Animal Center, Sichuan University, Chengdu 610040, Sichuan, China;
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Youcui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Hematology Research Laboratory, Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; and.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Gang
authors.initials: G
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Qianmei
authors.initials: Q
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Xueliang
authors.initials: X
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Immunology, College of Medicine, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Dechao
authors.initials: D
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; denghongx@scu.edu.cn.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology* / Q000627:therapeutic use; D015603:Keratinocytes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000096:biosynthesis; D058504:Th17 Cells / Q000187:drug effects / Q000502:physiology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; C532417:interleukin-35, human; D003907:Dexamethasone