scholarly journals PPAR Alpha Regulation of the Immune Response and Autoimmune Encephalomyelitis

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Yuhong Yang ◽  
Anne R. Gocke ◽  
Amy Lovett-Racke ◽  
Paul D. Drew ◽  
Michael K. Racke
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cells ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Steroid Hormone ◽  
Autoimmune Encephalomyelitis ◽  
Ppar Alpha ◽  
Nuclear Receptor Superfamily ◽  
Experimental Autoimmune

PPARs are members of the steroid hormone nuclear receptor superfamily and play an important role in the regulation of lipid metabolism, energy balance, artherosclerosis and glucose control. Recent studies suggest that they play an important role in regulating inflammation. This review will focus on PPAR-αregulation of the immune response. We describe how PPAR-αregulates differentiation of T cells by transactivation and/or interaction with other transcription factors. Moreover, PPAR-αagonists have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in mice, suggesting that they could provide a therapy for human autoimmune diseases such as multiple sclerosis.

scholarly journals TGF-β in Mice Ameliorates Experimental Autoimmune Encephalomyelitis in Regulating NK Cell Activity

2019 ◽  
Vol 28 (9-10) ◽  
pp. 1155-1160 ◽  
Author(s):  
J. Xu ◽  
Y. Wang ◽  
H. Jiang ◽  
M. Sun ◽  
J. Gao ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Nk Cells ◽  
Nk Cell ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

Multiple sclerosis is a disease characterized by inflammation and demyelination located in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is the most common animal model for multiple sclerosis (MS). Although the roles of T cells in MS/EAE have been well investigated, little is known about the functions of other immune cells in the neuroinflammation model. Here we found that an essential cytokine transforming growth factor β (TGF-β) which could mediate the differentiation of Th17/regulatory T cells was implicated in the natural killer (NK) cells’ activity in EAE. In EAE mice, TGF-β expression was first increased at the onset and then decreased at the peak, but the expressions of TGF-β receptors and downstream molecules were not affected in EAE. When we immunized the mice with MOG antigen, it was revealed that TGF-β treatment reduced susceptibility to EAE with a lower clinical score than the control mice without TGF-β. Consistently, inflammatory cytokine production was reduced in the TGF-β treated group, especially with downregulated pathogenic interleukin-17 in the central nervous system tissue. Furthermore, TGF-β could increase the transcription level of NK cell marker NCR1 both in the spleen and in the CNS without changing other T cell markers. Meanwhile TGF-β promoted the proliferation of NK cell proliferation. Taken together, our data demonstrated that TGF-β could confer protection against EAE model in mice through NK cells, which would be useful for the clinical therapy of MS.

scholarly journals Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis

Brain ◽  
2010 ◽  
Vol 133 (4) ◽  
pp. 1067-1081 ◽  
Author(s):  
Ingo Kleiter ◽  
Jian Song ◽  
Dominika Lukas ◽  
Maruf Hasan ◽  
Bernhard Neumann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
T Helper ◽  
T Helper 1 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

scholarly journals The Toll-like Receptor 2 (TLR2)-related Immunopathological Responses in the Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2019 ◽  
Author(s):  
Abdollah Jafarzadeh ◽  
Maryam Nemati ◽  
Hossain Khorramdelazad ◽  
Abbas Mirshafiey
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Wide Spectrum ◽  
Γδ T Cells ◽  
Type I ◽  
Autoimmune Encephalomyelitis ◽  
Amyloid A ◽  
Molecular Patterns ◽  
Experimental Autoimmune

Toll-like receptors (TLRs) play principle roles in recognition of autologous components which have been pointed as the danger-associated molecular patterns (DAMP) and microbial components which are identified as pathogen associated molecular patterns (PAMP).The infiltration of various inflammatory cells such as dendritic cells, lymphocytes (CD4+ T, CD8+ T as well as B cells), monocytes and macrophages occur into the central nervous sys­tem (CNS) during multiple sclerosis (MS) and its animal model named experimental autoimmune encephalomyelitis (EAE). The infiltrated leukocytes and residential cells of the CNS express several TLRs (especially TLR2) and their expression are elevated in MS and EAE. TLR2 recognizes a large variety DAMP and PAMP molecules due to its ability to create heterodimers with TLR1, TLR6 and probably TLR10. A wide spectrum of  DAMP molecules, including heat shock protein 60 (HSP60), HSP70, high mobility group box 1 (HMGB1), β-defensin 3, surfactant protein A and D, eosinophil-derived neurotoxin, gangliosides, serum amyloid A, hyaluronic acid and biglycan are identified by TLR2, whose their expression is increased in MS patients. TLR2 may contribute in the development of MS and EAE diseases through the reinforcement of Th1/Th17 cell-related responses, downregulation of regulatory T cells, induction of IL-17+ γδ T cells, inhibition of oligodendrocyte maturation, induction of poly ADP-ribose polymerase-1 (PARP-1)-dependent pathway in microglia, macrophages and astrocytes and inhibition of type I interferons expression. The contribution of TLR2-related immunopathological responses in the MS and EAE pathogenesis and its possible targeting as promising therapeutic potentials are considered in this review. 

scholarly journals The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Samuel S. Duffy ◽  
Justin G. Lees ◽  
Gila Moalem-Taylor
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Glial Cell ◽  
Cd4 T Cells ◽  
Killer Cell ◽  
Cell Subset ◽  
Cell Types ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE). MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.

scholarly journals IFP35 family proteins promote neuroinflammation and multiple sclerosis

2021 ◽  
Vol 118 (32) ◽  
pp. e2102642118
Author(s):  
Xizhong Jing ◽  
Yongjie Yao ◽  
Danning Wu ◽  
Hao Hong ◽  
Xu Feng ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Immune Cells ◽  
Neutralizing Antibodies ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Multiple Cells ◽  
Excessive Activation ◽  
Experimental Autoimmune

Excessive activation of T cells and microglia represents a hallmark of the pathogenesis of human multiple sclerosis (MS). However, the regulatory molecules overactivating these immune cells remain to be identified. Previously, we reported that extracellular IFP35 family proteins, including IFP35 and NMI, activated macrophages as proinflammatory molecules in the periphery. Here, we investigated their functions in the process of neuroinflammation both in the central nervous system (CNS) and the periphery. Our analysis of clinical transcriptomic data showed that expression of IFP35 family proteins was up-regulated in patients with MS. Additional in vitro studies demonstrated that IFP35 and NMI were released by multiple cells. IFP35 and NMI subsequently triggered nuclear factor kappa B–dependent activation of microglia via the TLR4 pathway. Importantly, we showed that both IFP35 and NMI activated dendritic cells and promoted naïve T cell differentiation into Th1 and Th17 cells. Nmi−/−, Ifp35−/−, or administration of neutralizing antibodies against IFP35 alleviated the immune cells’ infiltration and demyelination in the CNS, thus reducing the severity of experimental autoimmune encephalomyelitis. Together, our findings reveal a hitherto unknown mechanism by which IFP35 family proteins facilitate overactivation of both T cells and microglia and propose avenues to study the pathogenesis of MS.

scholarly journals Human gut derived Anaerotruncus colihominis ameliorates experimental autoimmune encephalomyelitis

2021 ◽  
Author(s):  
Paola Bianchimano ◽  
Graham J Britton ◽  
david Wallach ◽  
Emma Smith ◽  
Laura Cox ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Human Gut ◽  
Autoimmune Encephalomyelitis ◽  
Multiple Sclerosis Patients ◽  
Experimental Autoimmune

The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). The gut-brain axis refers to the complex interactions between the gut microbiota and the nervous and immune systems linking brain and gut functions. Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease hence making it a potential therapeutic target. Other studies have reported that long-term antibiotic therapy in multiple sclerosis patients reduces relapse rate and gadolinium enhancing lesions as well as improves measures of disability. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotics effects are not understood. Furthermore, there is no consensus on the gut derived bacterial strains that drive neuroinflammation in multiple sclerosis. Hence, it remains unclear how the gut microbiota can be targeted for therapeutic purposes in multiple sclerosis patients. Here we characterized the gut microbiome of untreated and vancomycin treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE and that this protective effect is mediated via the microbiota. Notably, we observed increase abundance of bacteria known to be strong inducers of regulatory T cells including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis which had a positive correlation with disease severity. Unexpectedly, we found that Anaerotruncus colihominis ameliorates EAE and this is associated with induction of RORγt+ regulatory T cells in the mesenteric lymph nodes. Together, our results identify vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease.

Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis

2016 ◽  
Vol 7 (3) ◽  
pp. 363-373 ◽  
Author(s):  
S. Stanisavljević ◽  
J. Lukić ◽  
M. Momčilović ◽  
M. Miljković ◽  
B. Jevtić ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Gut Microbiota ◽  
Lymphoid Tissue ◽  
Dark Agouti ◽  
Interleukin 17 ◽  
Mesenteric Lymph Nodes ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund’s adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer’s patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4+ T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-γ and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis.

The influence of sex hormones on cytokines in multiple sclerosis and experimental autoimmune encephalomyelitis: a review

2005 ◽  
Vol 11 (3) ◽  
pp. 349-359 ◽  
Author(s):  
Hans HLP van den Broek ◽  
Jan GMC Damoiseaux ◽  
Marc H De Baets ◽  
Raymond MM Hupperts
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cells ◽  
Regulatory T Cells ◽  
Sex Hormones ◽  
Inflammatory Cytokines ◽  
Cytokine Production ◽  
Anti Inflammatory ◽  
Experimental Autoimmune

The female predominance of multiple sclerosis (MS) has suggested that hormonal differences between the sexes must confer some protective effect on males or enhance the susceptibility of females to this disease. There has been evidence that gonadal hormones can modulate the immune response regulated by antigen presenting cells and T cells. These cells control the immune response by the production of interacting pro- and anti-inflammatory cytokines. The first include the acute phase pro-inflammatory cytokines of the innate immune response as well as the T-helper 1 (Th1) cytokines, while the later contain the Th2 cytokines as well as the suppressor cytokines. There is some evidence that MS and experimental autoimmune encephalitis (EAE) are Th1 cell-mediated diseases. For this reason many studies have been done to influence the pro-inflammatory cytokine production of these Th1 cells in favour of an anti-inflammatory immune response as mediated by Th2 cells. However the role of the regulatory T cells in this context is not clearly understood. Here we review the studies concerning the role of sex hormones on the cytokine production in relation to the disease course of MS and EAE and in particular in the light of the recent revival of the regulatory T cells and their suppressive cytokines.

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