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

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.

IL-20 receptor cytokines in autoimmune diseases

“…Li et al reported upregulated IL-19 and IL-20 gene expression in PBMC of patients with uveitis [66]. IL-24 was not included in this study, but Muls et al [67] reported that IL-24 (and IL-26) mRNA levels are comparable in relapsing or stable MS, and similar to healthy controls. Since autoreactive T cells are believed to participate in pathogenesis of both these diseases [68, 69], and in view of the reported ability of IL-20R cytokines to regulate T cells responses, further studies exploring the potential roles of IL-20R cytokines in CNS diseases would be of interest.…”

“…Li et al reported up-regulated IL-19 and IL-20 gene expressions in PBMC of patients with uveitis 66. IL-24 was not included in this study, but Muls et al67…”

Multiple Sclerosis: Immunopathology and Treatment Update

“…Of interest, anti-IL-17A humanized neutralizing monoclonal antibody (AIN457 or Secukinumab) injected in patients with MS showed reduction of lesions compared to placebo-treated control subjects [75]. In addition, Th22 cells are highly present in the peripheral blood and cerebral spinal fluid of patients with active RRMS [76], and IL-22 mRNA and Th22 cells are increased in relapsing MS compared to remitting MS patients [77]. Furthermore, Th22 cells specifically recognize MBP and are resistant to IFN-beta therapy [76].…”

Association of interleukin 22 gene polymorphisms and serum IL-22 level with risk of systemic lupus erythematosus in a Chinese population

“…The results indicate a new diagnosis and treatment target for SLE. There is evidence that IL-22 modulates the inflammatory process and several autoimmune diseases, including SLE, rheumatoid arthritis (RA) and multiple sclerosis (MS) [14][15][16]. In primary Sj€ ogren's syndrome (pSS), both protein and mRNA levels of IL-22 were increased significantly in the inflamed salivary glands.…”