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

<div><p>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 <i>ex vivo</i> or <i>in vitro</i>-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 <i>ex vivo</i> 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.</p>