IL-37 ameliorates the inflammatory process in psoriasis by suppressing proinflammatory cytokine production.

Abstract

IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A-transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A-transgenic mice were treated with plasmid coding human IL-37 sequence-formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.

• Authors: Xiu Teng, Zhonglan Hu, Xiaoqiong Wei, Zhen Wang, Ting Guan, Ning Liu, Xiao Liu, Ning Ye, Guohua Deng, Can Luo, Nongyu Huang, Changyan Sun, Minyan Xu, Xikun Zhou, Hongxin Deng, Carl Keith Edwards 3rd, Xiancheng Chen, Xiaoxia Wang, Kaijun Cui, Yuquan Wei, Jiong Li
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 192 Issue 4 Pg. 1815-23 (Feb 15 2014) ISSN: 1550-6606 [Electronic] United States
• PMID: 24453242 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• IL37 protein, human
• Interleukin-1
• Interleukin-6
• Interleukin-8
• Keratin-14
• Krt14 protein, mouse
• S100 Calcium Binding Protein A7
• S100 Proteins
• S100A7 protein, human
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse
• Interleukin-10
• Interferon-gamma

Topics

• Animals
• Cell Line
• Cell Proliferation
• Disease Models, Animal
• Down-Regulation
• Humans
• Immunologic Memory (immunology)
• Immunosuppression Therapy
• Inflammation (immunology)
• Interferon-gamma (genetics)
• Interleukin-1 (genetics, metabolism)
• Interleukin-10 (metabolism)
• Interleukin-6 (biosynthesis)
• Interleukin-8 (biosynthesis)
• Keratin-14 (genetics)
• Keratinocytes (immunology, metabolism)
• Macrophages (immunology)
• Mast Cells (immunology)
• Mice
• Mice, Transgenic
• Psoriasis (immunology, metabolism, pathology)
• S100 Calcium Binding Protein A7
• S100 Proteins (biosynthesis)
• Skin (immunology, pathology)
• T-Lymphocytes (immunology)
• Transfection
• Vascular Endothelial Growth Factor A (genetics)