title: Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells.
abstract: Immunoactivation is less evident in secondary progressive MS (SPMS) compared to relapsing-remitting disease. MicroRNA (miRNA) expression is integral to the regulation of gene expression; determining their impact on immune-related cell functions, especially CD4+ T cells, during disease progression will advance our understanding of MS pathophysiology. This study aimed to compare miRNA profiles of CD4+ T cells from SPMS patients to healthy controls (HC) using whole miRNA transcriptome next-generation sequencing (NGS). Total RNA was extracted from CD4+ T cells and miRNA expression patterns analyzed using Illumina-based small-RNA NGS in 12 SPMS and 12 HC samples. Results were validated in a further cohort of 12 SPMS and 10 HC by reverse transcription quantitative polymerase chain reaction (RT-qPCR).
  
  
  
  The ten most dysregulated miRNAs identified by NGS were selected for qPCR confirmation; five (miR-21-5p, miR-26b-5p, miR-29b-3p, miR-142-3p, and miR-155-5p) were confirmed to be down-regulated in SPMS (p < 0.05). SOCS6 is targeted by eight of these ten miRNAs. Consistent with this, SOCS6 expression is up-regulated in SPMS CD4+ T cells (p < 0.05). This is of particular interest as SOCS6 has previously been shown to act as a negative regulator of T cell activation.
  
  
  
  Ninety-seven percent of miRNA candidates identified by NGS were down-regulated in SPMS. The down-regulation of miRNAs and increased expression of SOCS6 in SPMS CD4+ T cells may contribute to reduced immune system activity in progressive MS.
authors: Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland 4226 Australia ; Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales 2305 Australia ; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308 Australia.
authors: Katherine A
authors: KA
authors: Sanders
authors: Institute of Health and Biomedical Innovation, Genomics Research Centre, Brisbane, Queensland 4059 Australia.
authors: Miles C
authors: MC
authors: Benton
authors: Institute of Health and Biomedical Innovation, Genomics Research Centre, Brisbane, Queensland 4059 Australia ; Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales 2305 Australia.
authors: Rod A
authors: RA
authors: Lea
authors: Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales 2305 Australia ; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308 Australia.
authors: Vicki E
authors: VE
authors: Maltby
authors: Department of Neurology, Division of Medicine, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310 Australia.
authors: Susan
authors: S
authors: Agland
authors: Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales 2305 Australia ; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308 Australia.
authors: Nathan
authors: N
authors: Griffin
authors: Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales 2305 Australia ; School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales 2308 Australia ; Division of Molecular Genetics, Pathology North, Newcastle, New South Wales 2305 Australia.
authors: Rodney J
authors: RJ
authors: Scott
authors: Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland 4226 Australia.
authors: Lotti
authors: L
authors: Tajouri
authors: Centre for Information-Based Medicine, Hunter Medical Research Institute, Newcastle, New South Wales 2305 Australia ; Department of Neurology, Division of Medicine, John Hunter Hospital, Locked Bag 1, Hunter Region Mail Centre, Newcastle, NSW 2310 Australia ; School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales 2308 Australia.
authors: Jeannette
authors: J
authors: Lechner-Scott
mesh_terms: D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
chemical_list: D035683:MicroRNAs; C473085:SOCS6 protein, human; D050826:Suppressor of Cytokine Signaling Proteins
keywords: CD4+ T cells; Immunology; MicroRNAs; Multiple sclerosis; Next-generation sequencing; Secondary progressive