A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseasesResearch in context
Yangyue Ni,
Ruiyan Xiong,
Yuxiao Zhu,
Ning Luan,
Chuanxin Yu,
Kun Yang,
Huiquan Wang,
Xuejun Xu,
Yuxuan Yang,
Siyu Sun,
Liyun Shi,
Jon Rob Padde,
Lin Chen,
Lu Chen,
Min Hou,
Zhipeng Xu,
Ren Lai,
Minjun Ji
Affiliations
Yangyue Ni
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Ruiyan Xiong
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Yuxiao Zhu
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Ning Luan
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, China
Chuanxin Yu
Jiangsu Institute of Parasitic Diseases, Wuxi, China
Kun Yang
Jiangsu Institute of Parasitic Diseases, Wuxi, China
Huiquan Wang
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Xuejun Xu
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Yuxuan Yang
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Siyu Sun
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Liyun Shi
Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, China
Jon Rob Padde
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Lin Chen
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Lu Chen
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Min Hou
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Zhipeng Xu
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China
Ren Lai
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, China; Corresponding author. Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, China.
Minjun Ji
Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China; Corresponding author. Department of Pathogen Biology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Jiangsu Province Engineering Research Center of Antibody Drug, Nanjing Medical University, Nanjing, China.
Summary: Background: Regulatory T cells (Tregs) can alleviate the development of autoimmune and inflammatory diseases, thereby proposing their role as a new therapeutic strategy. Parasitic helminths have co-evolved with hosts to generate immunological privilege and immune tolerance through inducing Tregs. Thus, constructing a “Tregs-induction”-based discovery pipeline from parasitic helminth is a promising strategy to control autoimmune and inflammatory diseases. Methods: The gel filtration chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC) were used to isolate immunomodulatory components from the egg extracts of Schistosoma japonicum. The extracted peptides were evaluated for their effects on Tregs suppressive functions using flow cytometry, ELISA and T cell suppression assay. Finally, we carried out colitis and psoriasis models to evaluate the function of Tregs induced by helminth-derived peptide in vivo. Findings: Here, based on target-driven discovery strategy, we successfully identified a small 3 kDa peptide (SjDX5-53) from egg extracts of schistosome, which promoted both human and murine Tregs production. SjDX5-53 presented immunosuppressive function by arresting dendritic cells (DCs) at an immature state and augmenting the proportion and suppressive capacity of Tregs. In mouse models, SjDX5-53 protected mice against autoimmune-related colitis and psoriasis through inducing Tregs and inhibiting inflammatory T-helper (Th) 1 and Th17 responses. Interpretation: SjDX5-53 exhibited the promising therapeutic effects in alleviating the phenotype of immune-related colitis and psoriasis. This study displayed a screening and validation pipeline of the inducer of Tregs from helminth eggs, highlighting the discovery of new biologics inspired by co-evolution of hosts and their parasites. Funding: This study was supported by the Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).
