NMI promotes the secretion of IL-17 and exacerbates psoriasis
Abstract
Damage-associated molecular patterns (DAMPs) are well established as key mediators of innate immune activation; however, their functions in modulating adaptive immunity, particularly T cell responses, remain incompletely characterized. Here, we report the identification and functional characterization of NMI—a recently identified DAMP—as a regulator of T helper 17 (Th17) cell activity and its involvement in psoriasis pathogenesis. Elevated expression of NMI was observed in psoriatic skin lesions and correlated significantly with heightened IL-17 levels. In a murine model of psoriasis, Nmi deficiency ( Nmi −/− ) resulted in a marked attenuation of skin inflammation, accompanied by significantly reduced expression of IL-17A and IL-17F. In vitro studies further demonstrated that NMI promotes the secretion of IL-17A and IL-17F from differentiated Th17 cells through its interaction with Toll-like receptor 4. Moreover, therapeutic neutralization of NMI using specific antibodies effectively ameliorated psoriatic symptoms in mice. Collectively, these results identify NMI as an endogenous enhancer of Th17-mediated immunity and highlight its potential as a therapeutic target in psoriasis.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (18)
Yaqi Gao
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University
Jingjing Wang
Zhen Qin
Zhongshan School of Medicine, Sun Yat-sen University
Na Xu
Jiangsu Collaborative Innovation Center of Biomedical Functional Materials, Nanjing Drum Tower Hospital, College of Chemistry and Materials Science
Xiaowen Wang
Tianqi Liu
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University
Shengli Wang
Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People’s Hospital (Zhuhai Clinical Medical College of Jinan University), Jinan University
Zhenxing Chen
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University
Yunhua Xu
Yongjie Yao
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University
Yimiao Wu
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University
Zhuangfeng Weng
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University
Yan Geng
Rheumatology and Clinical Immunology Department, Peking University First Hospital
Zhinan Yin
The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University
Jing Qin
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University
Tao Xu
Yingfang Liu
Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Sun Yat-sen University
Huanhuan Liang
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University