<b>Results:</b> The expression of IL-17, IL-23 P19, IL-23 P40, CCL20, CCL22 and CCR4 in spinal cord and serum IL-17 and IL-23 levels in PBS-administrated EAE mice were significantly increased compared with healthy group.
IL-17-producing T cells (Th17) have recently been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis.
IL-17 is the signature cytokine of recently discovered Th type 17 (Th17) cells, which are prominent in defense against extracellular bacteria and fungi as well as in autoimmune diseases, such as rheumatoid arthritis and experimental autoimmune encephalomyelitis in animal models.
IL-17-producing CD4(+) T cells (Th-17) contribute to the pathogenesis of experimental autoimmune encephalomyelitis and are associated with active disease in multiple sclerosis (MS).
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).
Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-γ+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats.
Also, histopathological damage (Caspase-3 and IL-17 activity, p ≤ .01) and cytokine levels (TNF-α and IL-1β, p < .01) were induced with EAE in mice brain tissue.
Although high levels of IFN-gamma are secreted in CIA and EAE, disease is exacerbated in IFN-gamma- or IFN-gamma receptor-deficient mice due to the ability of IFN-gamma to suppress IL-17 secretion.
Among T helper (Th) cell subsets differentiated from naive CD4<sup>+</sup> T cells, IL-17-producing Th17 cells are closely associated with the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and the MS animal model, experimental autoimmune encephalomyelitis (EAE).
Atypical EAE in DRB1*0301.DQ8.IFN-γ(-/-) mice was associated with increased encephalitogenicity of CD4 T cells and their ability to produce greater levels of IL-17 and GM-CSF compared with DRB1*0301.DQ8 mice.
Besides, proinflammatory cytokines such as, IFN-γ, TNF-α, IL-6, and IL-17 were significantly diminished in the serum and spinal cord of EAE mice receiving HIV-1 Tat clade B and C. Conversely, anti-inflammatory cytokines, including IL-10 and IL-4 were elevated in the serum and spinal cord of EAE mice receiving HIV Tat clade B and C when compared with the control group.
Both the percentage of Th17, and ratio of Th17/regulatory T (Treg), cells were elevated in miR-384-transfected EAE mice, which was consistent with the observed upregulation of expression of IL-17 and the Th17 lineage-specific transcription factor, RORγt.
Collectively, these findings indicate that decreased miR-497 expression is responsible for IL-17-triggered high HIF-1α expression and consequent IL-1β and IL-6 production by astrocytes in EAE mice.Cellular & Molecular Immunology advance online publication, 1 May 2017; doi:10.1038/cmi.2017.12.
Compared with nontransgenic mice, the CNS of AstroCD24TG mice had higher expression of cytokine genes such as IL-17 and demyelination-associated marker P8; the CNS of AstroCD24TG mice accumulated higher numbers of Th17 and total CD4+ T cells, whereas CD4+ T cells underwent more proliferation during EAE development.
Complementary in vivo studies in a mouse model showed that treatment with IFN-β enhanced expression of IL-27, and reduced IL-17 in the CNS and periphery and attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE).
Consistent with this, IL-17-induced inflammation is significantly reduced in <i>NDR1-</i>deficient mice, and NDR1 deficiency significantly protects mice from MOG-induced experimental autoimmune encephalomyelitis (EAE) and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis likely by its inhibition of IL-17-mediated signaling pathway.
Despite normal T cell priming, <i>Sb1</i><sup>-/-</sup> mice are resistant to EAE with a paucity of T helper (T<sub>H</sub>) cells that produce two or more of the cytokines, IFNγ, GM-CSF, and IL-17.
EAE mice with hMSC treatment on day 3 and day 12 had: (1) lower serum levels of IL-6, TNF-α (p < 0.0005), and IL-17 (p < 0.005 for day 3, p < 0.0005 for day 12); (2) reduced splenic cell production and secretion of IL-6, TNF-α (p < 0.05), and IL-17 (p < 0.05), and increased splenic production of IL-10; (3) reduced splenic Th17 cells (p < 0.05 for day 3, p < 0.005 for day 12), and (4) increased CD1d(high)CD5(+) regulatory B cells (p < 0.005) compared to EAE mice without hMSC treatment.
Eos(-/-) mice developed more severe experimental autoimmune encephalomyelitis than WT mice, displayed increased numbers of effector T cells in the periphery and CNS, and amplified IL-17 production.
Further analyses revealed that the antigenic presentations of both Mye-GalCer and its analog (AA2) in α-form via CD1d promoted IL-17 production from T cells, leading to elevated levels of IL-17 in EAE spinal cords and sera.