دورية أكاديمية
Causes and Consequences of miR-150-5p Dysregulation in Myasthenia Gravis.
العنوان: | Causes and Consequences of miR-150-5p Dysregulation in Myasthenia Gravis. |
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المؤلفون: | Cron MA; Center of Research in Myology, Sorbonne University, INSERM, Association Institute of Myology - UMRS 974, Paris, France., Maillard S; Center of Research in Myology, Sorbonne University, INSERM, Association Institute of Myology - UMRS 974, Paris, France., Truffault F; Center of Research in Myology, Sorbonne University, INSERM, Association Institute of Myology - UMRS 974, Paris, France., Gualeni AV; Department of Pathology and Laboratory Medicine, Istituto Nazionale dei Tumori, Milan, Italy., Gloghini A; Department of Pathology and Laboratory Medicine, Istituto Nazionale dei Tumori, Milan, Italy., Fadel E; Marie Lannelongue Hospital, Paris-Sud University, Le Plessis-Robinson, France., Guihaire J; Marie Lannelongue Hospital, Paris-Sud University, Le Plessis-Robinson, France., Behin A; Neuromuscular Disease Center, AIM, Pitié-Salpêtrière Hospital, AP-HP, Paris, France., Berrih-Aknin S; Center of Research in Myology, Sorbonne University, INSERM, Association Institute of Myology - UMRS 974, Paris, France., Le Panse R; Center of Research in Myology, Sorbonne University, INSERM, Association Institute of Myology - UMRS 974, Paris, France. |
المصدر: | Frontiers in immunology [Front Immunol] 2019 Mar 29; Vol. 10, pp. 539. Date of Electronic Publication: 2019 Mar 29 (Print Publication: 2019). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
مواضيع طبية MeSH: | B-Lymphocytes/*immunology , CD4-Positive T-Lymphocytes/*immunology , CD8-Positive T-Lymphocytes/*immunology , MicroRNAs/*immunology , Myasthenia Gravis/*immunology, Adolescent ; Adult ; Female ; Germinal Center/immunology ; Germinal Center/pathology ; Humans ; Male ; Myasthenia Gravis/pathology ; Proto-Oncogene Mas ; Proto-Oncogene Proteins c-myb/immunology ; Receptors, Nicotinic/immunology ; Thymus Gland/immunology ; Thymus Gland/pathology |
مستخلص: | Autoimmune Myasthenia gravis (MG) is a chronic neuromuscular disease mainly due to antibodies against the acetylcholine receptor (AChR) at the neuromuscular junction that induce invalidating muscle weaknesses. In early-onset MG, the thymus is the effector organ and is often characterized by B-cell infiltrations leading to ectopic germinal center (GC) development. The microRNA miR-150-5p has been previously characterized as a biomarker in MG due to its increase in the serum of patients and its decrease after thymectomy, correlated with an improvement of symptoms. Here, we investigated the causes and consequences of the miR-150 increase in the serum of early-onset MG patients. We observed that miR-150 expression was upregulated in MG thymuses in correlation with the presence of thymic B cells and showed by in situ hybridization experiments, that miR-150 was mainly expressed by cells of the mantle zone of GCs. However, we did not observe any correlation between the degree of thymic hyperplasia and the serum levels in MG patients. In parallel, we also investigated the expression of miR-150 in peripheral blood mononuclear cells (PBMCs) from MG patients. We observed that miR-150 was down-regulated, especially in CD4 + T cells compared to controls. These results suggest that the increased serum levels of miR-150 could result from a release from activated peripheral CD4 + T cells. Next, we demonstrated that the in vitro treatment of PBMCs with miR-150 or antimiR-150 oligonucleotides, respectively, decreased or increased the expression of one of its major target gene: the proto-oncogene MYB , a well-known actor of hematopoiesis. These results revealed that increased serum levels of miR-150 in MG patients could have a functional effect on PBMCs. We also showed that antimiR-150 caused increased cellular death of CD4 + and CD8 + T cells, along with the overexpression of pro-apoptotic genes targeted by miR-150 suggesting that miR-150 controlled the survival of these cells. Altogether, these results showed that miR-150 could play a role in MG both at the thymic level and in periphery by modulating the expression of target genes and peripheral cell survival. |
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فهرسة مساهمة: | Keywords: MYB; antimir-150; autoimmunity; germinal center; microRNA |
المشرفين على المادة: | 0 (MAS1 protein, human) 0 (MIRN150 microRNA, human) 0 (MYB protein, human) 0 (MicroRNAs) 0 (Proto-Oncogene Mas) 0 (Proto-Oncogene Proteins c-myb) 0 (Receptors, Nicotinic) |
تواريخ الأحداث: | Date Created: 20190416 Date Completed: 20200804 Latest Revision: 20211204 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC6450174 |
DOI: | 10.3389/fimmu.2019.00539 |
PMID: | 30984166 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1664-3224 |
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DOI: | 10.3389/fimmu.2019.00539 |