Analysis of coding and non-coding transcriptome of peripheral B cells reveals an altered interferon response factor (IRF)-1 pathway in multiple sclerosis patients

J Neuroimmunol. 2018 Nov 15:324:165-171. doi: 10.1016/j.jneuroim.2018.09.005. Epub 2018 Sep 15.

Abstract

Several evidences emphasize B-cell pathogenic roles in multiple sclerosis (MS). We performed transcriptome analyses on peripheral B cells from therapy-free patients and age/sex-matched controls. Down-regulation of two transcripts (interferon response factor 1-IRF1, and C-X-C motif chemokine 10-CXCL10), belonging to the same pathway, was validated by RT-PCR in 26 patients and 21 controls. IRF1 and CXCL10 transcripts share potential seeding sequences for hsa-miR-424, that resulted up-regulated in MS patients. We confirmed this interaction and its functional effect by transfection experiments. Consistent findings indicate down-regulation of IRF1/CXCL10 axis, that may plausibly contribute to a pro-survival status of B cells in MS.

Keywords: B cells; CXCL10 axis; Hsa-miR-424; IRF-1; Multiple Sclerosis; Transcriptome analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling / methods*
  • Humans
  • Interferon Regulatory Factor-1 / biosynthesis*
  • Interferon Regulatory Factor-1 / genetics
  • Male
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / metabolism*
  • Signal Transduction / physiology*
  • Transcriptome / physiology*

Substances

  • IRF1 protein, human
  • Interferon Regulatory Factor-1