A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases

  • EBioMedicine. 2023 Sep:95:104751. doi: 10.1016/j.ebiom.2023.104751.
Yangyue Ni  1 ,  Ruiyan Xiong  1 ,  Yuxiao Zhu  1 ,  Ning Luan  2 ,  Chuanxin Yu  3 ,  Kun Yang  3 ,  Huiquan Wang  1 ,  Xuejun Xu  1 ,  Yuxuan Yang  1 ,  Siyu Sun  1 ,  Liyun Shi  4 ,  Jon Rob Padde  1 ,  Lin Chen  1 ,  Lu Chen  1 ,  Min Hou  1 ,  Zhipeng Xu  1 ,  Ren Lai  5 ,  Minjun Ji  6
Affiliations
  • 1. Department of Pathogen Biology, National Vaccine Innovation Platform, Jiangsu Province Engineering Research Center of Antibody Drug, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
  • 2. 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.
  • 3. Jiangsu Institute of Parasitic Diseases, Wuxi, China.
  • 4. Institute of Translational Medicine, Zhejiang Shuren University, Hangzhou, China.
  • 5. 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. Electronic address: [email protected].
  • 6. Department of Pathogen Biology, National Vaccine Innovation Platform, Jiangsu Province Engineering Research Center of Antibody Drug, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
PMID: 37579625 DOI: 10.1016/j.ebiom.2023.104751
Abstract

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).

Keywords
Helminth-derived peptide; Inflammation; Target-driven discovery strategy; TolDCs; Treg.
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