ArticlePloS one2013
Kinetics of IL-6 production defines T effector cell responsiveness to regulatory T cells in multiple sclerosis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- <italic>Streptococcus pyogenes</italic> Infection and CD4Journal of innate immunity · 2026Article
- The Potential of β-Synuclein-Specific Regulatory T Cell Therapy as a Treatment for Progressive Multiple Sclerosis.International journal of molecular sciences · 2025Review
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- Effects of interleukin-6 signal inhibition on Treg subpopulations and association of Tregs with clinical outcomes in rheumatoid arthritis.Rheumatology (Oxford, England) · 2024Article
- Cancer and Autoimmune Diseases as Two Sides of Chronic Inflammation and the Method of Therapy.Current cancer drug targets · 2024Review
- A mathematical model and numerical simulation for SARS-CoV-2 dynamics.Scientific reports · 2023Article
- Tregs in transplantation tolerance: role and therapeutic potential.Frontiers in transplantation · 2023Review
- Bystander activation of microglia byFrontiers in immunology · 2023Article
- Boosting regulatory T cell function for the treatment of autoimmune diseases - That's only half the battle!Frontiers in immunology · 2022Review
- Interleukin-6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model.Immunity, inflammation and disease · 2021Article
- Treg-Resistant Cytotoxic CD4International journal of molecular sciences · 2021Article
- An evaluation of the recognised systemic inflammatory biomarkers of chronic sub-optimal inflammation provides evidence for inflammageing (IFA) during multiple sclerosis (MS).Immunity & ageing : I & A · 2021Review
- Genome-wide Identification and Analysis of Splicing QTLs in Multiple Sclerosis by RNA-Seq Data.Frontiers in genetics · 2021Article
- Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells.Frontiers in immunology · 2021Review
- Splenic Capture andACS nano · 2020Article
- Interleukin-6-knockdown of chimeric antigen receptor-modified T cells significantly reduces IL-6 release from monocytes.Experimental hematology & oncology · 2020Article
- CD8Nature communications · 2019Article
- ST2/MyD88 Deficiency Protects Mice against Acute Graft-versus-Host Disease and Spares Regulatory T Cells.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Abnormal effector and regulatory T cell subsets in paediatric-onset multiple sclerosis.Brain : a journal of neurology · 2019Article
Corrections and comments
- Erratum issuedLüssi, Felix [corrected to Luessi, Felix]
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In multiple sclerosis (MS) autoaggressive T effector cells (Teff) are not efficiently controlled by regulatory T cells (Treg) but the underlying mechanisms are incompletely understood. Proinflammatory cytokines are key factors facilitating Teff activity in chronic inflammation. Here we investigated the influence of IL-6 on Treg sensitivity of Teff from therapy-naïve MS patients with or without active disease. Compared to healthy volunteers and independent of disease course CD4(+) and especially CD8(+) MS-Teff were insensitive against functional active Treg from healthy controls. This unresponsiveness was caused by accelerated production of IL-6, elevated IL-6 receptor expression and phosphorylation of protein kinase B (PKB)/c-Akt in MS-Teff. In a positive feedback loop, IL-6 itself induced its accelerated synthesis and enhanced phosphorylation of PKB/c-Akt that finally mediated Treg resistance. Furthermore, accelerated IL-6 release especially by CD8(+) Teff prevented control of surrounding Teff, described here as "bystander resistance". Blockade of IL-6 receptor signaling or direct inhibition of PKB/c-Akt phosphorylation restored Treg responsiveness of Teff and prevented bystander resistance. In Teff of healthy controls (HC) exogenous IL-6 also changed the kinetics of IL-6 production and induced Treg unresponsiveness. This modulation was only transient in Teff from healthy volunteers, whereas accelerated IL-6 production in MS-Teff maintained also in absence of IL-6. Hence, we showed that the kinetics of IL-6 production instead of elevated IL-6 levels defines the Teff responsiveness in early Treg-T cell communication in MS independent of their disease course and propose IL-6 and associated PKB/c-Akt activation as effective therapeutic targets for modulation of Teff activity in MS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.