scholarly journals Pien Tze Huang Alleviates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mice by Regulating Th1 and Th17 Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Xuemei Qiu ◽  
Qingqing Guo ◽  
Xue Liu ◽  
Hui Luo ◽  
Danping Fan ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Relapsing Remitting ◽  
Pien Tze Huang ◽  
Experimental Autoimmune

CCDC134 ameliorated experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 cells

2018 ◽  
Vol 71 ◽  
pp. 158-168 ◽  
Author(s):  
Peng Xia ◽  
Xiaoting Gong ◽  
Lin Xiao ◽  
Yida Wang ◽  
Tianzhuo Zhang ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals 4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Wen-Tsan Weng ◽  
Ping-Chang Kuo ◽  
Dennis A. Brown ◽  
Barbara A. Scofield ◽  
Destin Furnas ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Immune Responses ◽  
Disease Progression ◽  
Disease Severity ◽  
Autoimmune Encephalomyelitis ◽  
Relapsing Remitting ◽  
Th17 Differentiation ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE. Methods Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice. Results Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro. Conclusions Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.

scholarly journals TLR4-RelA-miR-30a signal pathway regulates Th17 differentiation during experimental autoimmune encephalomyelitis development

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Xuebin Qu ◽  
Jingjing Han ◽  
Ying Zhang ◽  
Xingqi Wang ◽  
Hongbin Fan ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Signal Pathway ◽  
Autoimmune Encephalomyelitis ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Th17 Differentiation ◽  
Experimental Autoimmune

Abstract Background Toll-like receptor 4 (TLR4) is well known for activating the innate immune system; however, it is also highly expressed in adaptive immune cells, such as CD4+ T-helper 17 (Th17) cells, which play a key role in multiple sclerosis (MS) pathology. However, the function and governing mechanism of TLR4 in Th17 remain unclear. Methods The changes of TLR4 in CD4+ T cells from MS patients and experimental autoimmune encephalomyelitis (EAE) mice were tested. TLR4-deficient (TLR4−/−) naïve T cells were induced in vitro and transferred into Rag1−/− mice to measure Th17 differentiation and EAE pathology. DNA sequence analyses combining with deletion fragments and mutation analyses, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA) were used to explore the mechanism of TLR4 signaling pathway in regulating Th17 differentiation. Results The levels of TLR4 were increased in CD4+ Th17 cells both from MS patients and EAE mice, as well as during Th17 differentiation in vitro. TLR4−/− CD4+ naïve T cells inhibited their differentiation into Th17, and transfer of TLR4−/− CD4+ naïve T cells into Rag1−/− mice was defective in promoting EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. TLR4 signal enhanced Th17 differentiation by activating RelA, downregulating the expression of miR-30a, a negative regulator of Th17 differentiation. Inhibition of RelA activity increased miR-30a level, but decreased Th17 differentiation rate. Furthermore, RelA directly regulated the expression of miR-30a via specific binding to a conserved element of miR-30a gene. Conclusions TLR4−/− CD4+ naïve T cells are inadequate in differentiating to Th17 cells both in vitro and in vivo. TLR4-RelA-miR-30a signal pathway regulates Th17 differentiation via direct binding of RelA to the regulatory element of miR-30a gene. Our results indicate modulating TLR4-RelA-miR-30a signal in Th17 may be a therapeutic target for Th17-mediated neurodegeneration in neuroinflammatory diseases.

scholarly journals The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing—Remitting Multiple Sclerosis Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 748 ◽  
Author(s):  
Gabriele Di Sante ◽  
Susanna Amadio ◽  
Beatrice Sampaolese ◽  
Maria Elisabetta Clementi ◽  
Mariagrazia Valentini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Score ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune Encephalomyelitis Mouse ◽  
Extracellular Signaling ◽  
Relapsing Remitting ◽  
Inflammatory Processes ◽  
Experimental Autoimmune

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing–remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing–remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.

scholarly journals Mannan-conjugated myelin peptides prime non-pathogenic Th1 and Th17 cells and ameliorate experimental autoimmune encephalomyelitis

2015 ◽  
Vol 267 ◽  
pp. 254-267 ◽  
Author(s):  
Vivian Tseveleki ◽  
Theodore Tselios ◽  
Ioannis Kanistras ◽  
Olga Koutsoni ◽  
Maria Karamita ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune
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