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

Simple item page
dc.contributor.authorNi, Yangyue
dc.contributor.authorXiong, Ruiyan
dc.contributor.authorZhu, Yuxiao
dc.contributor.authorLuan, Ning
dc.contributor.authorYu, Chuanxin
dc.contributor.authorYang, Kun
dc.contributor.authorWang, Huiquan
dc.contributor.authorXu, Xuejun
dc.contributor.authorYang, Yuxuan
dc.contributor.authorSun, Siyu
dc.contributor.authorShi, Liyun
dc.contributor.authorChen, Lin
dc.contributor.authorChen, Lu
dc.contributor.authorHou, Min
dc.contributor.authorXu, Zhipeng
dc.contributor.authorLai, Ren
dc.contributor.authorJia, Minjun
dc.date.accessioned2024-03-05T22:19:15Z
dc.date.available2024-03-05T22:19:15Z
dc.date.issued2023-08-12
dc.description.abstractBackground: 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).en_US
dc.description.sponsorshipThe Natural Science Foundation of China (82272368) and Natural Science Foundation of Jiangsu Province (BK20211586).en_US
dc.identifier.citationNi, Y., Xiong, R. Z., Yuxiao... Padde, J. R., ...Jia, M. (2023). A target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases. EBioMedicine, 95. https://doi.org/10.1016/j.ebiom.2023.104751en_US
dc.identifier.urihttps://dir.muni.ac.ug/handle/20.500.12260/617
dc.language.isoenen_US
dc.publishereBioMedicineen_US
dc.subjectHelminth-derived peptideen_US
dc.subjectTarget-driven discovery strategyen_US
dc.subjectTregen_US
dc.subjectTolDCsen_US
dc.subjectInflammationen_US
dc.titleA target-based discovery from a parasitic helminth as a novel therapeutic approach for autoimmune diseases.en_US
dc.typeArticleen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Padde_2023_Article_1.pdf
Size:
7.03 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Research Articles