Fingolimod Increases CD39-Expressing Regulatory T Cells in Multiple Sclerosis Patients
(2014) PLoS One — Vol. 9, n° 11, p. e113025 [1-7] (2014)
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- BACKGROUND: Multiple sclerosis (MS) likely results from an imbalance between regulatory and inflammatory immune processes. CD39 is an ectoenzyme that cleaves ATP to AMP and has been suggested as a novel regulatory T cells (Treg) marker. As ATP has numerous proinflammatory effects, its degradation by CD39 has anti-inflammatory influence. The purpose of this study was to explore regulatory and inflammatory mechanisms activated in fingolimod treated MS patients. METHODS AND FINDINGS: Peripheral blood mononuclear cells (PBMCs) were isolated from relapsing-remitting MS patients before starting fingolimod and three months after therapy start. mRNA expression was assessed in ex vivo PBMCs. The proportions of CD8, B cells, CD4 and CD39-expressing cells were analysed by flow cytometry. Treg proportion was quantified by flow cytometry and methylation-specific qPCR. Fingolimod treatment increased mRNA levels of CD39, AHR and CYP1B1 but decreased mRNA expression of IL-17, IL-22 and FOXP3 mRNA in PBMCs. B cells, CD4+ cells and Treg proportions were significantly reduced by this treatment, but remaining CD4+ T cells were enriched in FOXP3+ cells and in CD39-expressing Tregs. CONCLUSIONS: In addition to the decrease in circulating CD4+ T cells and CD19+ B cells, our findings highlight additional immunoregulatory mechanisms induced by fingolimod.
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Muls, N., Dang, H. A., Sindic, C., & Van Pesch, V. (2014). Fingolimod Increases CD39-Expressing Regulatory T Cells in Multiple Sclerosis Patients. PLoS One, 9(11), e113025 [1-7]. https://doi.org/10.1371/journal.pone.0113025 (Original work published 2014)