Nathalie G V Muls1, Hong Anh Dang1, Christian J M Sindic1, Vincent van Pesch2. 1. Unité de Neurochimie, Institute of Neuroscience, Université catholique de Louvain, Belgium. 2. Unité de Neurochimie, Institute of Neuroscience, Université catholique de Louvain, Belgium vincent.vanpesch@uclouvain.be.
Abstract
BACKGROUND: Accumulating data highlight proinflammatory processes leading to MS relapses. Whether anti-inflammatory mechanisms are concomitantly activated is unclear. The ectonucleotidase CD39 has been described as a novel T regulatory cell (Treg) marker. The purpose of this study was to explore whether regulatory mechanisms are activated during MS relapses and reinforced by intravenous methylprednisolone (ivMP). METHODS: Blood samples were collected from stable and relapsing MS patients and healthy controls. We used FOXP3 methylation-specific qPCR and CD4(+)CD25(high)FOXP3(+) analysis to quantify Tregs. Cytokine mRNA expression levels were measured in peripheral blood mononuclear cells (PBMCs) and in CD4(+) T cells. CD39 expression was determined by flow cytometry in monocytes, NK, T and B cells. CD39 enzymatic activity was assessed by ATP luminometry. RESULTS: The proportion of Tregs was similar in relapsing MS patients and healthy controls. CD39 mRNA level was higher in PBMCs of relapsing MS patients than in controls. The proportion of CD39-expressing Tregs was higher in MS patients. IvMP decreased the overall proportion of Tregs while it increased CD39 mRNA levels, the proportions of CD39-expressing Tregs and monocytes as well as CD39 ectonucleotidase activity. CONCLUSIONS: Our data suggest that immunoregulatory mechanisms are ongoing in MS patients, particularly during relapses, and strengthened by ivMP.
BACKGROUND: Accumulating data highlight proinflammatory processes leading to MS relapses. Whether anti-inflammatory mechanisms are concomitantly activated is unclear. The ectonucleotidase CD39 has been described as a novel T regulatory cell (Treg) marker. The purpose of this study was to explore whether regulatory mechanisms are activated during MS relapses and reinforced by intravenous methylprednisolone (ivMP). METHODS: Blood samples were collected from stable and relapsing MSpatients and healthy controls. We used FOXP3 methylation-specific qPCR and CD4(+)CD25(high)FOXP3(+) analysis to quantify Tregs. Cytokine mRNA expression levels were measured in peripheral blood mononuclear cells (PBMCs) and in CD4(+) T cells. CD39 expression was determined by flow cytometry in monocytes, NK, T and B cells. CD39 enzymatic activity was assessed by ATP luminometry. RESULTS: The proportion of Tregs was similar in relapsing MSpatients and healthy controls. CD39 mRNA level was higher in PBMCs of relapsing MSpatients than in controls. The proportion of CD39-expressing Tregs was higher in MSpatients. IvMP decreased the overall proportion of Tregs while it increased CD39 mRNA levels, the proportions of CD39-expressing Tregs and monocytes as well as CD39 ectonucleotidase activity. CONCLUSIONS: Our data suggest that immunoregulatory mechanisms are ongoing in MSpatients, particularly during relapses, and strengthened by ivMP.
Authors: Cristina Ulivieri; Domiziana De Tommaso; Francesca Finetti; Barbara Ortensi; Giuliana Pelicci; Mario Milco D'Elios; Clara Ballerini; Cosima T Baldari Journal: Front Immunol Date: 2019-05-10 Impact factor: 7.561
Authors: Nuria Álvarez-Sánchez; Ivan Cruz-Chamorro; María Díaz-Sánchez; Patricia Judith Lardone; Juan Miguel Guerrero; Antonio Carrillo-Vico Journal: Sci Rep Date: 2019-02-19 Impact factor: 4.379