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

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

doi:10.1016/j.ebiom.2023.104751

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. Epub 2023 Aug 12.

Authors

Yangyue Ni¹, Ruiyan Xiong¹, Yuxiao Zhu¹, Ning Luan², Chuanxin Yu³, Kun Yang³, Huiquan Wang¹, Xuejun Xu¹, Yuxuan Yang¹, Siyu Sun¹, Liyun Shi⁴, Jon Rob Padde¹, Lin Chen¹, Lu Chen¹, Min Hou¹, Zhipeng Xu¹, Ren Lai⁵, Minjun Ji⁶

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: rlai@mail.kiz.ac.cn.
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: jiminjun@njmu.edu.cn.

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.

MeSH terms

Animals
Autoimmune Diseases* / therapy
Colitis*
Humans
Mice
Psoriasis*
Schistosoma japonicum*
T-Lymphocytes, Regulatory