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.
We have recently reported the association of a polymorphic intronic CA-repeat in the interferon-gamma gene (IFNG) with gender bias in susceptibility to multiple sclerosis (MS) in a Sardinian population.
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.
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.
We detected a significant positive correlation between TNF-alpha (r=0.55) and interferon-gamma (r=0.54) mRNA expression and the BDI sum scores during an acute attack in MS patients.
We detected a significant positive correlation between TNF-alpha (r=0.55) and interferon-gamma (r=0.54) mRNA expression and the BDI sum scores during an acute attack in MS patients.
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.
Using transient transfection assays, we observed that the MS-detrimental cytokines TNFalpha, interferon-gamma, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-beta is inhibitory.
Using genetic knockouts, we demonstrate that loss of endogenous miR-29, derived from the miR-29ab1 genomic cluster, results in unrestrained T-bet expression and IFN-γ production. miR-29b regulates T-bet and IFN-γ via a direct interaction with the 3' untranslated regions, and IFN-γ itself enhances miR-29b expression, establishing a novel regulatory feedback loop. miR-29b is increased in memory CD4(+) T cells from multiple sclerosis (MS) patients, which may reflect chronic Th1 inflammation.
To study the possible role of tumor necrosis factor-alpha G-308A, interleukin-6 G-174C, interleukin-10 C-592A, C-819T, G-1082A, transforming growth factor (TGF)-beta (codons 10 and 25), and interferon-gammaT+874A polymorphisms in susceptibility to MS in Iranian population, DNA samples from 98 patients and 97 healthy controls were genotyped using polymerase chain reaction-sequence-specific primers.
To evaluate how in vivo intravenous methylprednisolone treatment in patients with MS could influence transmigration of PBMNCs in an in vitro model; to perform transmigration experiments through a methylprednisolone-treated endothelium with PBMNCs from untreated healthy control subjects to evaluate putative selective effects of corticosteroids on endothelium; concomitantly, to quantify the concentration of matrix metalloproteinases 2 and 9 in supernatants of PBMNCs and in serum samples from methylprednisolone-treated patients with MS; to evaluate monokine induced by interferon-gamma release in the supernatants of human umbilical vein endothelial cells treated with interferon-gamma alone or interferon-gamma and methylprednisolone; and to perform gene expression studies of matrix metalloproteinases 2 and 9 in human umbilical vein endothelial cells and PBMNCs from methylprednisolone-treated patients with MS.
To assess whether SNPs within genes for relevant cytokines and their receptors modulate the associations of TNF-α and IFN-γ with relapse, thus providing additional information about these cytokine effects and the roles of these genes in MS.
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.
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.
There are mononuclear cells in blood and cerebrospinal fluid of patients with MS that produce interferon-gamma and interleukin-4 in response to myelin basic protein (MBP) and proteolipid protein (PLP).
The levels of IFN-gamma and IL-4 mRNA-positive cells in MS after culture in the presence of AChR, and in MG after culture in the presence of MBP or PLP, did not differ from those detected after culture without antigen.
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).
The aim of this study was to investigate whether polymorphisms in the IFNG and IFNGR1 and IFNGR2 genes are associated with susceptibility to MS, or disease characteristics, as defined by clinical and imaging criteria.
Specifically, MS-like lesions developed in the brain that included equal numbers of IFN-γ producing CD4(+) and CD8(+) T cells and demyelination, none of which is observed in MOG induced EAE.
Several observations suggest that the interferon system may be of interest in the study of MS development To investigate whether polymorphism in components of the IFN system and the JAK-STAT pathway influence susceptibility to MS, we performed a linkage analysis between polymorphic loci in or close to the IFN gamma, IFN gamma receptor, IFN alpha/beta receptor, JAK 1, STAT 1 and STAT 3 genes in 27 Swedish families with at least two members having MS. Tests for transmission disequilibrium and nonparametric linkage analysis gave negative results.
Results showed that: 1) CD19+/TNFα+, CD19+/IL-12+ and CD19+/IFNγ+ lymphocytes are significantly increased in primary progressive (PP) compared to secondary progressive (SP), relapsing-remitting (RR), benign (BE) MS and HC; 2) CD19+/IL-6+ lymphocytes are significantly increased in PP, SP and RR compared to BEMS and HC; and 3) CD19+/IL-13+, CD19+/IL-10+, and CD19+/IL-10+/TGFβ+ (Bregs) B lymphocytes are reduced overall in MS patients compared to HC.