The Role of miR-155 in Modulating Gene Expression in CD4+ T Cells: Insights into Alternative Immune Pathways in Autoimmune Encephalomyelitis

Int J Mol Sci. 2024 Oct 22;25(21):11355. doi: 10.3390/ijms252111355.

Abstract

CD4+ T cells are considered the main orchestrators of autoimmune diseases. Their disruptive effect on CD4+ T cell differentiation and the imbalance between T helper cell populations can be most accurately determined using experimental autoimmune encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). One epigenetic factor known to promote autoimmune inflammation is miRNA-155 (miR-155), which is significantly upregulated in inflammatory T cells. The aim of the present study was to profile the transcriptome of immunized mice and determine their gene expression levels based on mRNA and miRNA sequencing. No statistically significant differences in miRNA profile were observed; however, substantial changes in gene expression between miRNA-155 knockout (KO) mice and WT were noted. In miR-155 KO mice, mRNA expression in CD4+ T cells changed in response to immunization with the myeloid antigen MOG35-55. After restimulation with MOG35-55, increased Ffar1 (free fatty acid receptor 1) and Scg2 (secretogranin-2) expression were noted in the CD4+ T cells of miR-155-deficient mice; this is an example of an alternative response to antigen stimulation.

Keywords: CD4+ T cells; KO mice; MOG; autoimmune disorders; experimental autoimmune encephalomyelitis (EAE); immunization; miR-155.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • Encephalomyelitis, Autoimmune, Experimental* / genetics
  • Encephalomyelitis, Autoimmune, Experimental* / immunology
  • Encephalomyelitis, Autoimmune, Experimental* / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • MicroRNAs* / genetics
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Transcriptome

Substances

  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Myelin-Oligodendrocyte Glycoprotein

Grants and funding

This research was funded by National Science Centre Poland, grant number SONATA 2015/17/D/NZ6/04245.