Dataset Information

Expression of T cell-related lncRNAs in multiple sclerosis.

ABSTRACT: Long non-coding RNAs (lncRNAs) have been demonstrated to in the pathophysiology of multiple sclerosis (MS). In order to appraise the role of T cell-related lncRNAs in this disorder, we assessed expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR in MS patients and healthy individuals. We detected significant difference in the expression of RMRP and FLICR between cases and controls. There were substantial correlations between expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR lncRNAs among patients, but not controls. The strongest correlations were found between RMRP and TH2-LCR, and between MAFTRR and RMRP with correlation coefficients of 0.69 and 0.59, respectively. ROC curve analysis revealed appropriate power of FLICR in differentiating between MS patients and healthy controls (AUC value = 0.84). Expression of NEST lncRNA was positively correlated with disease duration in MS patients, but negatively correlated with age at onset. In brief, we reported dysregulation of two T cell-related lncRNAs in MS patients and proposed FLICR as a putative marker for this disorder.

SUBMITTER: Dadyar M

PROVIDER: S-EPMC9461285 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Expression of T cell-related lncRNAs in multiple sclerosis.

Dadyar Maryam M Hussen Bashdar Mahmud BM Eslami Solat S Taheri Mohammad M Emadi Farhad F Ghafouri-Fard Soudeh S Sayad Arezou A

Frontiers in genetics 20220826

Long non-coding RNAs (lncRNAs) have been demonstrated to in the pathophysiology of multiple sclerosis (MS). In order to appraise the role of T cell-related lncRNAs in this disorder, we assessed expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR in MS patients and healthy individuals. We detected significant difference in the expression of RMRP and FLICR between cases and controls. There were substantial correlations between expressions of NEST, RMRP, TH2-LCR, MAFTRR and FLICR lncRNAs among pat ...[more]

PMID: 36092928

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Project description:Although fingolimod and interferon-β are two mechanistically different multiple sclerosis (MS) treatments, they both induce B cell activating factor (BAFF) and shift the B cell pool towards a regulatory phenotype. However, whether there is a shared mechanism between both treatments in how they influence the B cell compartment remains elusive. In this study, we collected a cross-sectional study population of 112 MS patients (41 untreated, 42 interferon-β, 29 fingolimod) and determined B cell subsets, cell-surface and RNA expression of BAFF-receptor (BAFF-R) and transmembrane activator and cyclophilin ligand interactor (TACI) as well as plasma and/or RNA levels of BAFF, BAFF splice forms and interleukin-10 (IL-10) and -35 (IL-35). We added an in vitro B cell culture with four stimulus conditions (Medium, CpG, BAFF and CpG+BAFF) for untreated and interferon-β treated patients including measurement of intracellular IL-10 levels. Our flow experiments showed that interferon-β and fingolimod induced BAFF protein and mRNA expression (P ≤ 3.15 x 10-4) without disproportional change in the antagonizing splice form. Protein BAFF correlated with an increase in transitional B cells (P = 5.70 x 10-6), decrease in switched B cells (P = 3.29 x 10-4), and reduction in B cell-surface BAFF-R expression (P = 2.70 x 10-10), both on TACI-positive and -negative cells. TACI and BAFF-R RNA levels remained unaltered. RNA, plasma and in vitro experiments demonstrated that BAFF was not associated with increased IL-10 and IL-35 levels. In conclusion, treatment-induced BAFF correlates with a shift towards transitional B cells which are enriched for cells with an immunoregulatory function. However, BAFF does not directly influence the expression of the immunoregulatory cytokines IL-10 and IL-35. Furthermore, the post-translational mechanism of BAFF-induced BAFF-R cell surface loss was TACI-independent. These observations put the failure of pharmaceutical anti-BAFF strategies in perspective and provide insights for targeted B cell therapies.

Dataset Information

Expression of T cell-related lncRNAs in multiple sclerosis.

Publications

Expression of T cell-related lncRNAs in multiple sclerosis.

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