| Autor: |
Johansson, Alina, Nyberg, William A, Sjöstrand, Maria, Moruzzi, Noah, Bergman, Petra, Khademi, Mohsen, Andersson, Magnus, Piehl, Fredrik, Berggren, Per‐Olof, Covacu, Ruxandra, Jagodic, Maja, Espinosa, Alexander |
| Zdroj: |
European Journal of Immunology; Feb2019, Vol. 49 Issue 2, p313-322, 10p |
| Abstrakt: |
Systemic autoimmune diseases are characterized by the overexpression of type I IFN stimulated genes, and accumulating evidence indicate a role for type I IFNs in these diseases. However, the underlying mechanisms for this are still poorly understood. To explore the role of type I IFN regulated miRNAs in systemic autoimmune disease, we characterized cellular expression of miRNAs during both acute and chronic type I IFN responses. We identified a T cell‐specific reduction of miR‐31‐5p levels, both after intramuscular injection of IFNβ and in patients with Sjögren's syndrome (SjS). To interrogate the role of miR‐31‐51p in T cells we transfected human CD4+ T cells with a miR‐31‐5p inhibitor and performed metabolic measurements. This identified an increase in basal levels of glucose metabolism after inhibition of miR‐31‐5p. Furthermore, treatment with IFN‐α also increased the basal levels of human CD4+ T‐cell metabolism. In all, our results suggest that reduced levels of miR‐31‐5p in T cells of SjS patients support autoimmune T‐cell responses during chronic type I IFN exposure. Quiescent and naive T cells depend on oxidative phosphorylation but switch to glycolysis during their effector stage. We identified miR‐31‐5p as a type I IFN‐suppressed miRNA that negatively regulates glycolysis in human CD4+ T cells. This suggests that miR‐31‐5p regulates T‐cell metabolism in autoimmune diseases with type I IFN signatures. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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