Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.856694
Keywords
multiple sclerosis (MS) disease; T helper 17 cell (Th17 cell); parthenolide (PTL); nuclear factor kappa B (NF-kappa B); experimental autoimmune encephalomyelitis (EAE); retinoid-related orphan receptor-gamma t (ROR gamma t)
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Funding
- National Natural Science Foundation of China [82171042, 81870651]
- Natural Science Foundation of Tianjin [20JCZDJC00100]
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This study demonstrates the important immunosuppressive effect of parthenolide (PTL) on autoimmune inflammation. PTL can alleviate clinical symptoms by inhibiting inflammatory cell infiltration, reducing inflammation, and demyelination. It also regulates the immune response by inhibiting the reactivation of specific T cells and the differentiation of CD4(+) T cells into pathogenic Th17 cells.
T helper (Th) cells play crucial roles in inflammation and adaptive immune system. Importantly, Th17 cells, a major pathogenic Th cell subset, are involved in the pathogenesis of multiple sclerosis (MS) and its classical animal modal experimental autoimmune encephalomyelitis (EAE). Previous studies have shown that parthenolide (PTL), a sesquiterpene lactone, possesses potent anti-cancer and anti-inflammatory activities. However, the immunosuppressive effect of PTL on the pathogenic Th17 cell and MS is unclear. In this study, we showed that PTL treatment could alleviate clinical symptoms by inhibiting inflammatory cell infiltration, reducing inflammation and demyelination of CNS. In addition, the mRNA expression of cytokines and inflammatory factors in CD4(+) T cells, especially Th1 and Th17 cells, reduced in both CNS and peripheral immune tissue of EAE mice. Furthermore, PTL could inhibit the reactivation of MOG-specific T cells and the differentiation of naive CD4(+) T cells into Th17 cells in vitro. We also found that PTL inhibited nuclear factor kappa B (NF-kappa B) signaling and retinoid-related orphan receptor-gamma t (ROR gamma t) in mouse Th17 cell and human Jurkat cell line. Taken together, our data demonstrated a critical immune-suppressive effect of PTL on autoimmune inflammation through regulating Th17 cells and the NF-kappa B/ROR gamma t pathway.
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