IL-37 ameliorates the inflammatory process in psoriasis by suppressing proinflammatory cytokine production.
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.
State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China;
Xiu
X
Teng
Zhonglan
Z
Hu
Xiaoqiong
X
Wei
Zhen
Z
Wang
Ting
T
Guan
Ning
N
Liu
Xiao
X
Liu
Ning
N
Ye
Guohua
G
Deng
Can
C
Luo
Nongyu
N
Huang
Changyan
C
Sun
Minyan
M
Xu
Xikun
X
Zhou
Hongxin
H
Deng
Carl Keith
CK
Edwards
Xiancheng
X
Chen
Xiaoxia
X
Wang
Kaijun
K
Cui
Yuquan
Y
Wei
Jiong
J
Li
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D053547:Keratin-14 / Q000235:genetics; D015603:Keratinocytes / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011565:Psoriasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000096:biosynthesis; D012867:Skin / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
C508609:IL10 protein, human; C508587:IL37 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D053547:Keratin-14; C507446:Krt14 protein, mouse; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016753:Interleukin-10; D007371:Interferon-gamma