摘要
Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4^(+)T cell subsets.Despite advancements in the management of multiple sclerosis,there is a critical need for more effective and safer treatments.In the present study,we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis-an animal model of multiple sclerosis-and evaluated its effects on pathogenic CD4^(+)T cell activation both in vivo and in vitro.Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis,as demonstrated by reduced demyelination and neuroinflammation.Moreover,Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression.Lycium barbarum glycopeptide also modulated pathogenic CD4^(+)T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion.Notably,no side effects were observed,suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide.Furthermore,RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1,an essential regulator of T cell activation and differentiation.This finding was supported by the reversal of T helper/T helper 17 cell response suppression upon AP-1 blockade.Collectively,these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4^(+)T cell-associated autoimmune or inflammatory diseases,such as multiple sclerosis.
基金
supported by the National Natural Science Foundational of China,Nos.U24A20692(to CJZ),82371355(to CJZ),and 82101414(to MH)
National NaturalScience Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)
Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)
The Innovationand Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)
Funding for Distinguished Young Scholars of Sichuan Provincial People’sHospital,No.30420230005
Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(toCJZ)
Sichuan Science and Technology Support Project,No.2023YFS0212(to BH)
Project of Sichuan Provincial Health Commission,No.19PJ265(to LD).
