IL-22, GM-CSF and IL-17 in peripheral CD4+ T cell subpopulations during multiple sclerosis relapses and remission. Impact of corticosteroid therapy

PLoS One. 2017 Mar 16;12(3):e0173780. doi: 10.1371/journal.pone.0173780. eCollection 2017.

Abstract

Multiple sclerosis (MS) is thought to be a Th17-mediated dysimmune disease of the central nervous system. However, recent publications have questioned the pathogenicity of IL-17 per se and rather suggest the implication of other Th17-related inflammatory mediators. Therefore, we studied the expression of GM-CSF, IL-22, IL-24, IL-26 and CD39 in peripheral blood mononuclear cells (PBMCs) from MS patients during relapses, remission and following corticosteroid treatment. We performed qPCR to measure mRNA levels from ex vivo or in vitro-stimulated PBMCs. Cytokine levels were determined by ELISA. We used flow cytometry to assess GM-CSF+, IL-22+ and CD39+ cells in relationship to IL-17+ CD4+ T cells. Our results showed that IL-22 mRNA and IL-22+CD4+ lymphocytes are increased in circulating cells of relapsing MS patients compared to remitting patients while GM-CSF was unchanged. We have further shown that 12.9, 39 and 12.4% of Th17 cells from MS patients during relapses expressed IL-22, GM-CSF and CD39 respectively. No changes in these proportions were found in stable MS patients. However, the majority of GM-CSF+ or IL-22+ T cells did not co-express IL-17. GM-CSF mRNA, but not IL-22 mRNA, was dramatically decreased ex vivo by ivMP. Our results contribute to a better characterisation of Th17, Th22 and ThGM-CSF cells in the setting of MS and according to disease activity.

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use*
  • Adult
  • Case-Control Studies
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / blood*
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Interleukin-17 / blood*
  • Interleukin-22
  • Interleukins / blood*
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / pathology
  • RNA, Messenger / blood
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Interleukin-17
  • Interleukins
  • RNA, Messenger
  • Granulocyte-Macrophage Colony-Stimulating Factor

Grants and funding

This work was supported by the Fonds National de la Recherche Scientifique (www.fnrs.be), Bayer educational grants and the Belgian Charcot Foundation (www.fondation-charcot.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.