miR‐31 regulates energy metabolism and is suppressed in T cells from patients with Sjögren's syndrome

Abstract

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.Keywords: Autoimmunity r Interferons r Immune regulation r Metabolism r Rheumatology Additional supporting information may be found online in the Supporting Information section at the end of the article.by the overexpression of a large set of IFN-stimulated genes (ISGs) collectively termed the IFN signature [1,2]. Type I IFNs signal through the heterodimeric IFNA receptor and induce the expression of ISGs, several of which have important antiviral * These authors contributed equally.

RETRACTED ARTICLE: Mirt2 functions in synergy with miR-377 to participate in inflammatory pathophysiology of Sjögren's syndrome

“…microRNAs (miRs) have been identified as the noncoding RNAs and found to participate in the progression and management of the inflammatory response [8]. Increasing evidence have elucidated that miRs are associated with inflammation in SS patients [9][10][11]. Besides, miR-377 has been found to mediate the proliferation and apoptosis progresses as well as DNA methylation in several malignancies [12][13][14].…”

miR-31-NUMB Cascade Modulates Monocarboxylate Transporters to Increase Oncogenicity and Lactate Production of Oral Carcinoma Cells

“…In previous studies, miR-31 was shown to target SIRT3 to inhibit mitochondrial activity [7] and target ACOX1 to disrupt the lipidome profile in OSCC [8]. Other studies reported that miR-31 modulated the metabolic profile by targeting different types of cells [10,11,37]. As NUMB is the direct target of miR-31 and several other oncogenic miRNAs [23,25,26], findings in this work substantiated that miR-31 is an oncogenic miRNA that also modulates complex metabolic regulation in OSCC [7,8].…”

MicroRNA expression profile of Lacrimal Glands in rabbit autoimmune dacryoadenitis model

“…As for SS, previous studies reported that miR-335 was upregulated in the minor salivary gland of SS patients, and its expression level was inversely proportional to the unstimulated salivary flow rate [26]. In addition, Johansson et al identified miR-31 was reduced in the T cells of SS patients, which supports the autoimmune T cell response during chronic type I IFN exposure [27]. These findings were consistent with our results that miR-335-3p was upregulated, whereas miR-31-5p was downregulated in autoimmune dacryoadenitis rabbits compared to the controls, suggesting these miRs may play a potential role in the pathogenesis of autoimmune dry eye.…”