A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases
Ni, YY; Xiong, RY; Zhu, YX; Luan, N; Yu, CX; Yang, K; Wang, HQ; Xu, XJ; Yang, YX; Sun, SY; Shi, LY; Padde, JR; Chen, L; Chen, L; Hou, M; Xu, ZP; Lai, R; Ji, MJ
2023
发表期刊EBIOMEDICINE
ISSN2352-3964
卷号95
摘要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.
收录类别SCI
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/14142
专题科研部门_天然药物功能蛋白质学科组(赖仞)
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GB/T 7714
Ni, YY,Xiong, RY,Zhu, YX,et al. A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases[J]. EBIOMEDICINE,2023,95.
APA Ni, YY.,Xiong, RY.,Zhu, YX.,Luan, N.,Yu, CX.,...&Ji, MJ.(2023).A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases.EBIOMEDICINE,95.
MLA Ni, YY,et al."A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases".EBIOMEDICINE 95(2023).
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