We confirm the pathogenicity of IL-22BP in both rat and mouse models of MS and go on to suggest a pathogenic mechanism involving lack of IL-22-mediated inhibition of T cell-derived IFN-γ expression.
Therefore, we hypothesize that ERβ-selective agonists inhibit MHC II expression in microglia via inhibition of class II trans-activator (CIITA) expression by a mechanism involving inhibition of the translocation of IFNγ regulatory factor (IRF-1) to the nucleus, thereby inhibiting the inflammatory response and symptoms in the MS model.
This study demonstrates that T-bet<sup>high</sup> IgG1<sup>+</sup> B cells are triggered by IFNγ and TLR9 signals, likely contributing to enhanced CXCR3-mediated recruitment and local reactivity in the CNS of MS patients.ANN NEUROL 2019;86:264-278.
This activity is independent of MHC class-I mediated inhibition via KIR2DL1, but dependent upon the interaction between NK cell-expressed KIR2DL4 and its oligodendrocyte-expressed ligand, HLA-G. NK cells from patients with MS express higher levels of IFN-γ following conjugation to OLs, more actively promote in vitro reduction of MOG and MAG and have higher frequencies of the KIR2DL4 positive population.
Furthermore, GSTT1-AS1 (r = 0.313, p = 0.027) and (IFNG r = 0.478, p < 0.0001) demonstrated a significant positive correlation with age at onset.Briefly, the current study provided for the first time dysregulation of GSTT1-AS1 and IFNG-AS lncRNAs network in MS, which highlights the significant role of epigenetic pathways in this autoimmune disorder.
We previously demonstrated that decreased expression of miR-140-5p was associated with the progression of multiple sclerosis (MS) and miR-140-5p targeted STAT1 and interfered with the expression of IFN-γ.
Peripheral blood mononuclear cells (PBMCs) from natalizumab treated persons with MS (n = 52) and healthy controls (HCs) (n = 24) were analyzed by IFNγ/IL-22/IL-17A FluoroSpot.
IFN-γ secreting Th1 cells and IL-17 secreting Th17 cells are found to play key roles in autoimmune diseases like multiple sclerosis (MS) and ulcerative colitis (UC).
In other inflammatory demyelinating disorders, such as multiple sclerosis, the expression of heat shock proteins (HSPs) in combination with interferon-γ (IFN-γ) has been suggested to play a prominent role in the initiation of demyelination and inflammation.
The importance that the T helper (Th)1 cytokine, interferon γ (IFN-γ), and the Th17 cytokine, interleukin (IL)-17, play in MS pathogenesis is indicated by recent clinical trial data by the enhanced presence of Th1/Th17 cells in central nervous system (CNS) tissue, cerebrospinal fluid (CSF), and blood, and by research on animal models of MS, such as experimental autoimmune encephalomyelitis (EAE).
Proinflammatory cytokines such as interleukin-17 (IL-17), IL-22, tumor necrosis factor-α, IL-1, IL-12 and interferon-γ may cause MS through several signaling pathways.
Here, we identify an imbalance between the cytokines IFN-γ and IL-10 as a shared T<sub>reg</sub> signature present in patients with multiple sclerosis and under high-salt conditions.
Interferon-γ (IFN-γ) has been implicated in the pathogenesis of multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE).
Importantly, in MS the proportion of IFNγ- and GM-CSF-secreting T cells expressing CCR6 was significantly enriched in the CSF, and was elevated in MS, suggesting these cells play a pathogenic role in this disease.
We explored the correlation between concentrations of Aβ<sub>1-42</sub> and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients.
It is postulated herein that the detrimental activation of autoimmune T cells by glutamate in MS could lead to: (1) Cytotoxicity in the CNS: T cell-mediated killing of neurons and glia cells, which would subsequently increase the extracellular glutamate levels, and by doing so increase the excitotoxicity mediated by excess glutamate, (2) Release of proinflammatory cytokines, e.g., TNFα and IFNγ that increase neuroinflammation.
Here, we report that glial STAT1 and -3 are distinctively phosphorylated following the interaction of activated lymphocytes and glia, and this effect is significantly inhibited by glatiramer acetate (GA), a disease-modifying drug for MS. GA also reduces the activations of STAT1 and -3 by MS-associated stimuli such as IFNγ or LPS in primary glia, but not neurons.
Fish oil is claimed to improve outcome in multiple sclerosis (MS) through anti-inflammatory and antioxidant effects by reducing cytokines including TNF-α, IFN-γ, IL6, and IL-1β.
We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients.