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.
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.
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.
IL-17-producing CD4(+) T (Th17) cells, along with IFN-γ-expressing Th1 cells, represent two major pathogenic T cell subsets in experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS).
Previous studies in mouse models of MS demonstrated that IFN-γ and IL-17 regulate lesion localization within the brain; however, the mechanisms by which these cytokines mediate their effects have not been identified.
Post-mortem cerebrospinal fluid and dissected cerebral leptomeningeal tissue from patients with multiple sclerosis were used to study the presence of tumour necrosis factor and interferon gamma protein and messenger RNA levels.
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.
Recent studies in new EAE models, especially in transgenic ones, have in connection with new analytical techniques such as microarray assays provided a deeper insight into the pathogenic cellular and molecular mechanisms of EAE and potentially of MS. For example, it was possible to better delineate the role of soluble pro-inflammatory (tumor necrosis factor-α, interferon-γ and interleukins 1, 12 and 23), anti-inflammatory (transforming growth factor-β and interleukins 4, 10, 27 and 35) and neurotrophic factors (ciliary neurotrophic factor and brain-derived neurotrophic factor).
Likewise, the male-specific protective association of interferon-gamma (IFNG) SNP rs2069727 in MS was replicated with the same sex specificity in childhood ALL (OR = 0.6, 95% CI = 0.4-1.0, Mantel-Haenszel P = 0.03).
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.
In order to investigate the role of some proinflammatory cytokines (interleukin (IL)-2, IL-12, and interferon-gamma (IFN-gamma)) as a risk factor for MS, this study was performed.
Recent studies have better defined the association between the human leukocyte antigen (HLA)-DR, cytotoxic T-lymphocyte antigen-4, interleukin-7 receptor, and interferon-gamma polymorphisms and susceptibility to multiple sclerosis (MS), while many more studies have been added to the controversial pool of likely false-positive and false-negative genetic association and linkage studies.
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.
CXCL10 (interferon-gamma-inducible protein-10) levels are increased in cerebrospinal fluid of multiple sclerosis (MS) patients with symptomatic attacks of inflammatory demyelination, supporting a role for this molecule in MS pathogenesis.
Interferon-gamma mRNA attenuates its own translation by activating PKR: a molecular basis for the therapeutic effect of interferon-beta in multiple sclerosis.
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.
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.
As for the T-cell characterization, CD4+ anti-alpha B-crystallin T cells secreting high levels of interferon-gamma are similarly identified in MS and healthy donors.