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

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. Th...

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Detalles Bibliográficos
Autores principales: Ni, Yangyue, Xiong, Ruiyan, Zhu, Yuxiao, Luan, Ning, Yu, Chuanxin, Yang, Kun, Wang, Huiquan, Xu, Xuejun, Yang, Yuxuan, Sun, Siyu, Shi, Liyun, Padde, Jon Rob, Chen, Lin, Chen, Lu, Hou, Min, Xu, Zhipeng, Lai, Ren, Ji, Minjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10448429/
https://www.ncbi.nlm.nih.gov/pubmed/37579625
http://dx.doi.org/10.1016/j.ebiom.2023.104751
Descripción
Sumario: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 10.13039/501100001809Natural Science Foundation of China (82272368) and 10.13039/501100004608Natural Science Foundation of Jiangsu Province (BK20211586).