scholarly journals Kirenol Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Differentiation of Th1 and Th17 Cells and Inducing Apoptosis of Effector T Cells

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Juan Xiao ◽  
Rongbing Yang ◽  
Lin Yang ◽  
Xiaohang Fan ◽  
Wenwei Liu ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Th17 Cells ◽  
Effector T Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

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.

Interferon-β is a key regulator of proinflammatory events in experimental autoimmune encephalomyelitis

2010 ◽  
Vol 16 (12) ◽  
pp. 1458-1473 ◽  
Author(s):  
CL Galligan ◽  
LM Pennell ◽  
TT Murooka ◽  
E Baig ◽  
B Majchrzak-Kita ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Lymph Nodes ◽  
Th17 Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Disease Onset ◽  
Rapid Progression ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Background: Interferon (IFN)-β is an effective therapy for relapsing-remitting multiple sclerosis, yet its mechanism of action remains ill-defined. Objectives: Our objective was to characterize the role of IFN-β in immune regulation in experimental autoimmune encephalomyelitis (EAE). Methods: IFN-β +/+ and IFN-β—/— mice were immunized with myelin oligodendrocyte glycoprotein peptide in the presence or absence of IFN-β, to induce EAE. Disease pathogenesis was monitored in the context of incidence, time of onset, clinical score, and immune cell activation in the brains, spleens and lymph nodes of affected mice. Results: Compared with IFN-β+/+ mice, IFN-β—/ — mice exhibited an earlier onset and a more rapid progression of EAE, increased numbers of CD11b+ leukocytes infiltrating affected brains and an increased percentage of Th17 cells in the central nervous system and draining lymph nodes. IFN-β treatment delayed disease onset and reduced disease severity. Ex vivo experiments revealed that the lack of IFN-β results in enhanced generation of autoreactive T cells, a likely consequence of the absence of IFN-β-regulated events in both the CD4+ T cells and antigen-presenting dendritic cells. Gene expression analysis of IFN-β-treated bone marrow macrophages (CD11b +) identified modulation of genes affecting T cell proliferation and Th17 differentiation. Conclusions: We conclude that IFN-β acts to suppress the generation of autoimmune-inducing Th17 cells during the development of disease as well as modulating pro-inflammatory mediators.

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