Ni, YangyueXiong, RuiyanZhu, YuxiaoLuan, NingYu, ChuanxinYang, KunWang, HuiquanXu, XuejunYang, YuxuanSun, SiyuShi, LiyunChen, LinChen, LuHou, MinXu, ZhipengLai, RenJia, Minjun2024-03-052024-03-052023-08-12Ni, 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.2023.104751https://dir.muni.ac.ug/handle/20.500.12260/617Background: 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).enHelminth-derived peptideTarget-driven discovery strategyTregTolDCsInflammationArticle