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Background <p>Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. The prevalence of MS is increasing annually, but its etiology and pathogenesis remain unclear. Exosomes which carry various bioactive substances from parent cells, serve as carriers of immunoregulatory factors. Exosomes derived from MSCs and Tregs have been shown to alleviate clinical symptoms in the experimental autoimmune encephalomyelitis (EAE) model. Therefore, we tried to evaluate the functions of Th2 cell-derived exosomes in EAE model and explore the mechanisms.</p> Methods and results <p>Female C57BL/6 mice were randomly divided into control group, EAE group and EAE + Th2-exos group. Mice in EAE + Th2-exos group were injected with Th2-exosomes on day 16 after EAE induction, and samples were collected 48&#xa0;h later. Compared to EAE group, Th2-exosome treatment significantly reduced the neurological behavior scores and alleviated inflammatory infiltration and vacuolation in the spinal cord. Exosomes downregulated the ratio of M1 microglia, Th1 and Th17 cells, while the ratio of M2 microglia and Th2 cells was upregulated. Additionally, serum levels of pro-inflammatory cytokines (including IL-1β, IL-6, and TNF-α, primarily secreted by microglia) were significantly reduced, and the expression levels of proteins related to the NLRP3 inflammasome and NF-κB signaling pathway (P-P65, Caspase-1 p20, Cleaved-IL-1β, and NLRP3) decreased notably. The P-P65/P65 ratio was significantly lower.</p> Conclusion <p>Th2-exosomes may alleviate MS clinical symptoms by inhibiting microglial activation through the suppression of the NLRP3 inflammasome and NF-κB signaling pathways, thereby reducing central nervous system inflammation.</p>

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Th2 cell-derived exosomes alleviate central nervous system inflammation and demyelination in experimental autoimmune encephalomyelitis by regulating inflammasomes to inhibit microglia activation

  • 期刊论文

  • 发表日期：

    2025年11月15日

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  • Xianmin Cao,
  • Yufen Peng,
  • Shimin Liu,
  • Chao Zhou,
  • Liang Gao,
  • Jiajun Xiong,
  • Meihong Zhou,
  • Mengqi Xia,
  • Yingqiong Xiong

摘要

Background

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. The prevalence of MS is increasing annually, but its etiology and pathogenesis remain unclear. Exosomes which carry various bioactive substances from parent cells, serve as carriers of immunoregulatory factors. Exosomes derived from MSCs and Tregs have been shown to alleviate clinical symptoms in the experimental autoimmune encephalomyelitis (EAE) model. Therefore, we tried to evaluate the functions of Th2 cell-derived exosomes in EAE model and explore the mechanisms.

Methods and results

Female C57BL/6 mice were randomly divided into control group, EAE group and EAE + Th2-exos group. Mice in EAE + Th2-exos group were injected with Th2-exosomes on day 16 after EAE induction, and samples were collected 48 h later. Compared to EAE group, Th2-exosome treatment significantly reduced the neurological behavior scores and alleviated inflammatory infiltration and vacuolation in the spinal cord. Exosomes downregulated the ratio of M1 microglia, Th1 and Th17 cells, while the ratio of M2 microglia and Th2 cells was upregulated. Additionally, serum levels of pro-inflammatory cytokines (including IL-1β, IL-6, and TNF-α, primarily secreted by microglia) were significantly reduced, and the expression levels of proteins related to the NLRP3 inflammasome and NF-κB signaling pathway (P-P65, Caspase-1 p20, Cleaved-IL-1β, and NLRP3) decreased notably. The P-P65/P65 ratio was significantly lower.

Conclusion

Th2-exosomes may alleviate MS clinical symptoms by inhibiting microglial activation through the suppression of the NLRP3 inflammasome and NF-κB signaling pathways, thereby reducing central nervous system inflammation.