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T follicular helper (Tfh) cells are a subpopulation of activated CD4\u2009+\u2009T cells, while T follicular regulatory (Tfr) cells, a novel subset of Treg cells, possess specialized abilities to suppress the Tfh-GC response and inhibit antibody production. Dysregulation of either Tfh or Tfr cells has been implicated in the pathogenesis of MS. However, the molecular mechanism underlying the anti-inflammatory effects of MP therapy on experimental autoimmune encephalomyelitis (EAE), a representative model for MS, remains unclear. This study aimed to investigate the effects of MP treatment on EAE and elucidate the possible underlying molecular mechanisms involed. We evaluated the effects of MP on disease progression, CNS inflammatory cell infiltration and myelination, microglia and astrocyte activation, as well as Tfr\/Tfh ratio and related molecules\/inflammatory factors in EAE mice. Additionally, Western blotting was used to assess the expression of proteins associated with the PI3K\/AKT pathway. Our findings demonstrated that MP treatment ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Furthermore, it reduced microglial and astrocytic activation. MP may increase the number of Tfr cells and the levels of cytokine TGF-\u03b21, while reducing the number of Tfh cells and the levels of cytokine IL-21, as well as regulate the imbalanced Tfr\/Tfh ratio in EAE mice. The PI3K\/AKT\/FoxO1 and PI3K\/AKT\/mTOR pathways were found to be involved in EAE development. However, MP treatment inhibited their activation. MP reduced neuroinflammation in EAE by regulating the balance between Tfr\/Tfh cells via inhibition of the PI3K\/AKT\/FoxO1 and PI3K\/AKT\/mTOR signalling pathways.<\/jats:p>","DOI":"10.1007\/s10753-024-02099-y","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T00:01:51Z","timestamp":1720483311000},"page":"950-962","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Methylprednisolone Modulates the Tfr\/Tfh ratio in EAE-Induced Neuroinflammation through the PI3K\/AKT\/FoxO1 and PI3K\/AKT\/mTOR Signalling Pathways"],"prefix":"10.1007","volume":"48","author":[{"given":"Nan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongliang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuezhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,9]]},"reference":[{"key":"2099_CR1","doi-asserted-by":"publisher","unstructured":"Lassmann, H. 2018. 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