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Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens new research avenues
- Source :
- Autoimmunity Reviews, Autoimmunity Reviews, Elsevier, 2018, 17 (6), pp.588-600. ⟨10.1016/j.autrev.2018.01.008⟩, Autoimmunity Reviews, 2018, 17 (6), pp.588-600. ⟨10.1016/j.autrev.2018.01.008⟩
- Publication Year :
- 2018
- Publisher :
- Elsevier B.V., 2018.
-
Abstract
- International audience; In early-onset Myasthenia Gravis (MG) with anti-acetylcholine receptor antibodies, thymic abnormalities associated with ectopic germinal centers are frequent. miRNAs by acting as post-transcriptional regulators are involved in autoimmunity. To investigate the implication of miRNAs in thymic changes associated with early-onset MG, we performed a miRnome study and data were analyzed with different approaches. miRNAs of interest were further investigated by RT-PCR and transfection experiments for functional tests.First, analyzing specific dysregulated miRNAs, we focused our attention on miR-7-5p and miR-125a-5p, and confirmed by RT-PCR their respective down- and up-regulation in MG thymuses. miR-7 was the most down-regulated thymic miRNA in MG and we observed an inverse correlation between its expression and CCL21 mRNA expression. We next showed that miR-7 down-regulation was due to thymic epithelial cells and by transfecting these cells with miR-7, we demonstrated that it controlled CCL21 release. As CCL21 is essential for germinal center development, we suggested that miR-7 could be involved in thymic changes associated with MG. miR-125a was up-regulated in MG thymuses and is of great interest as it is known to regulate FoxP3 expression, and to modulate the different inflammatory signaling pathways.Thanks to this thymic miRnome study, we also showed the specific dysregulation of miRNA clusters. In particular, we observed that miRNAs localized at the extremity of the X chromosome were down-regulated. This effect seemed linked to their close localization to the fragile X mental retardation 1 gene (FMR1) and the DNA methylation status.Altogether, this miRnome analysis demonstrated that specific thymic miRNAs can be associated with MG and provides novel insights into the pathogenesis of MG.
- Subjects :
- 0301 basic medicine
Biomedical Research
Immunology
Thymus Gland
Biology
WDR1
03 medical and health sciences
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]
microRNA
Myasthenia Gravis
medicine
Immunology and Allergy
Humans
miRnome
FMR1
Chemokine CCL21
Germinal center
miR-7
Transfection
miR-125
medicine.disease
Myasthenia gravis
3. Good health
MicroRNAs
030104 developmental biology
Autoimmunity, Myasthenia Gravis, microRNA, Transcriptomes
Gene Expression Regulation
DNA methylation
Cancer research
[SDV.IMM]Life Sciences [q-bio]/Immunology
Signal transduction
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
CCL21
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 15689972
- Database :
- OpenAIRE
- Journal :
- Autoimmunity Reviews, Autoimmunity Reviews, Elsevier, 2018, 17 (6), pp.588-600. ⟨10.1016/j.autrev.2018.01.008⟩, Autoimmunity Reviews, 2018, 17 (6), pp.588-600. ⟨10.1016/j.autrev.2018.01.008⟩
- Accession number :
- edsair.doi.dedup.....cd7b8b555f6ad72ee6fba935608386e4