Upregulation of IL-17, but not of IL-9, in circulating cells of CIS and relapsing MS patients. Impact of corticosteroid therapy on the cytokine network

Muls, Nathalie; Jnaoui, Karima; Dang, Hong Anh; Wauters, Antony; Snick, Jacques Van; Sindic, Christian; Pesch, Vincent Van

doi:10.1016/j.jneuroim.2011.12.010

Cited by 27 publications

(25 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…52 Interestingly, T-helper cell 17 (T H 17) cytokines such as IL-17A, IL-6 and IL-23p19, 53,54 the levels of which are elevated during NMO exacerbations, are downregulated by corticosteroids. 55 In addition to a direct role in removing pathogenic AQP4-IgG, plasma exchange could similarly reduce levels of proinflammatory cytokines, alter the numbers of T cells and B cells, and modify T H -cell phenotypes. 56 …”

Section: Current Therapiesmentioning

confidence: 99%

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

2014

View full text Add to dashboard Cite

Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood–brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19—all initially developed for other indications—are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood–brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date.

show abstract

Section: Current Therapiesmentioning

confidence: 99%

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

2014

View full text Add to dashboard Cite

show abstract

“…Watanabe et al observed that the annual relapse rate was dramatically lower under use of corticosteroids than the period without the drug and it was also observed that the odds ratio for the period with 10 mg/day or less was 8.71 compared with more than 10 mg/day [110]. The elevated levels of Th17 cytokines such as IL-17A, IL-6 and IL-23p, which are elevated during NMO exacerbations, are downregulated by corticosteroids [111].…”

Section: Treatment Strategiesmentioning

confidence: 99%

Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review

Pereira

Reiche

Kallaur

et al. 2015

Journal of the Neurological Sciences

View full text Add to dashboard Cite

The aim of this study was to review the epidemiological and clinical characteristics of neuromyelitis optica (NMO) and the immunopathological mechanisms involved in the neuronal damage. NMO is an inflammatory demyelinating autoimmune disease of the central nervous system that most commonly affects the optic nerves and spinal cord. NMO is thought to be more prevalent among non-Caucasians and where multiple sclerosis (MS) prevalence is low. NMO follows a relapsing course in more than 80-90% of cases, which is more commonly in women. It is a complex disease with an interaction between host genetic and environmental factors and the main immunological feature is the presence of anti-aquaporin 4 (AQP4) antibodies in a subset of patients. NMO is frequently associated with multiple other autoantibodies and there is a strong association between NMO with other systemic autoimmune diseases. AQP4-IgG can cause antibody-dependent cellular cytotoxicity (ADCC) when effector cells are present and complement-dependent cytotoxicity (CDC) when complement is present. Acute therapies, including corticosteroids and plasma exchange, are designed to minimize injury and accelerate recovery. Several aspects of NMO pathogenesis remain unclear. More advances in the understanding of NMO disease mechanisms are needed in order to identify more specific biomarkers to NMO diagnosis.

show abstract

“…Their therapeutic effects are related to multiple immunosuppressive mechanisms, acting in various ways to decrease cytokine production, immune cell extravasation and to induce apoptosis. In the setting of MS relapses, GC could have a dual role, by inhibiting proinflammatory processes [17], but also by increasing the production of anti-inflammatory molecules such as CD39, IL-10 and TGF-β [18–20]. …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Upregulation of IL-17, but not of IL-9, in circulating cells of CIS and relapsing MS patients. Impact of corticosteroid therapy on the cytokine network

Cited by 27 publications

References 52 publications

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

Treatment of neuromyelitis optica: state-of-the-art and emerging therapies

Epidemiological, clinical, and immunological characteristics of neuromyelitis optica: A review

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

Contact Info

Product

Resources

About