Gene expression signature of Lewis rats with experimental NMO and controls
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE73411 | GEO | 2016/03/22
SECONDARY ACCESSION(S): PRJNA296899
REPOSITORIES: GEO
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Project description:study was performed to reveal the extent to which NMO-IgG contributes to tissue damage in experimental NMO Gene expression was studied in Lewis rats after transfer of myelin basic protein-specific T cells on day 0 and NMO-IgG on day 4. The animals were sacrificed 24 hours later. Controls did either not receive T cells (0), did receive control IgG or PBS instead of NMO-IgG, or were left completely untreated.
2016-03-22 | E-GEOD-73411 | biostudies-arrayexpress
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2024-01-17 | GSE235277 | GEO
Project description:Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that primarily affects the spinal cord and optic nerves in the central nervous system (CNS). It is characterized by the presence of immunoglobulin G (IgG) antibodies against aquaporin 4, a protein found in astrocytes (known as NMO-IgG). Monocytes/macrophages and microglia accumulate at the active injury sites and contribute to the disease process. However, it is unclear whether these active cells originate from circulating monocytes/macrophages or resident microglia. Recent studies have investigated the role of microglia/macrophages in multiple sclerosis (MS) using specific microglial markers, such as P2ry12 and Tmem119, and have shown that active cells are derived from microglia. In contrast, the function of monocyte/macrophages and microglia in NMO has not been extensively studied. Therefore, this study aims to analyze the functions of monocytes/macrophages and microglia using microglial markers (P2ry12 and Tmem119) in an NMO-like mouse model and evaluate their role in the pathophysiology of NMO.
2024-01-17 | GSE235276 | GEO
Project description:Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.
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Project description:Genome sequence of Buchnera aphidicola Nmo (Nipponaphis monzeni)
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Project description:Guillain-Barré syndrome (GBS) is characterized by acute immune-mediated peripheral neuropathy, which may result in rapidly progressive paralysis and fatal respiratory failure. As the underlying pathological mechanisms of GBS are unclear, we surveyed the transcriptome of rats with experimental autoimmune neuritis (EAN), a model of GBS. Briefly, sciatic nerves on both sides were collected from 8–10-week-old Lewis rats during early (10 days post-induction), peak (19 days), and late neuritis (30 days). Total RNA was sequenced to identify differentially expressed genes. Compared to control rats without induced neuritis, 33 genes were differentially expressed in the early phase (14 upregulated and 19 downregulated), with an adjusted P-value < 0.05 and |log2 fold-change| > 1, as were 137 genes in the peak phase (126 upregulated and 11 downregulated) and 60 genes in the late phase (58 upregulated and 2 downregulated). Eleven of these genes were common to all stages, suggesting their crucial roles throughout the disease course. Analysis of protein-protein interactions revealed Fos, Ccl2, Itgax and C3 as node genes at different stages. Functional analysis of differentially expressed genes identified biological processes and pathways that are activated as neuritis progresses. This is the first genome-wide gene expression study of peripheral nerves in experimental autoimmune neuritis model. Dynamic gene expression and significantly altered biological functions were detected in different phases of the disease, increasing our understanding of the molecular mechanisms underlying EAN and highlighting potential targets for its diagnosis and treatment.
2020-01-22 | GSE133750 | GEO
Project description:Probiotics beneficial effects on the host are associated with regulation of the intestinal microbial homeostasis and with modulation of inflammatory immune responses in the gut and in periphery. In this study, we investigated the clinical efficacy of two lactobacillus and two bifidobacterium probiotic strains in experimental autoimmune myasthenia gravis (EAMG) and experimental autoimmune encephalomyelitis (EAE) models, induced in Lewis rats. Treatment with probiotics led to less severe disease manifestation in both models; ex vivo analyses showed preservation of neuromuscular junction in EAMG and myelin content in EAE spinal cord. Immunoregulatory transcripts were found differentially expressed in gut associated lymphoid tissue and in peripheral immunocompetent organs. Feeding EAMG animals with probiotics resulted in increased levels of Transforming Growth Factor-β (TGFβ) in serum, and increased percentages of regulatory T cells (Treg) in peripheral blood leukocyte. Exposure of immature dendritic cells to probiotics induced their maturation toward an immunomodulatory phenotype, and secretion of TGFβ. Our data showed that bifidobacteria and lactobacilli treatment effectively modulates disease symptoms in EAMG and EAE models, and support further investigations to evaluate their use in autoimmune diseases.
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Project description:This study aimed to determine the effect and roles of microRNA (miRNA, miR) treatment in experimental autoimmune anterior uveitis (EAAU).Uveitis was induced in Lewis rats by simultaneous injections of bovine melanin-associated antigen into the hind footpad and the intraperitoneal cavity. The animals were injected intravitreally with low-dose (0.5??g) or high-dose (1.5??g) miR-146a. The clinical scores, leukocyte count in the aqueous humor, and histology were assessed. Cytokine changes were evaluated by relative mRNA expression and enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-?B) was assessed by immunofluorescence and Western blotting. Evaluation of the DNA-binding activity of NF-?B was performed by electrophoretic mobility shift assay (EMSA).Treatment with miR-146a significantly attenuated clinical scores and leukocyte infiltration in a dose-dependent manner, a result that was compatible with histological findings. Following miR-146a injections, downregulation of interleukin- (IL-) 1?, IL-6, and IL-12 and interferon- (IFN-) ? and upregulation of IL-10 and IL-17 were noted. The decreased NF-?B expression on immunofluorescence and Western blotting and reduced DNA-binding activity on EMSA were demonstrated following miR-146a treatment.miR-146a effectively reduced intraocular inflammation in EAAU through the inhibition of NF-?B. miR-146a might be a new treatment choice for uveitis.
| S-EPMC5757132 | biostudies-literature
Project description:Beneficial effects of probiotics on gut microbiota homeostasis and inflammatory immune responses suggested the investigation of their potential clinical efficacy in experimental models of autoimmune diseases. Indeed, administration of two bifidobacteria and lactobacilli probiotic strains prevented disease manifestations in the Lewis rat model of Myasthenia Gravis (EAMG). Here, we demonstrate the clinical efficacy of therapeutic administration of vital bifidobacteria (i.e., from EAMG onset). The mechanisms involved in immunomodulation were investigated with ex vivo and in vitro experiments. Improvement of EAMG symptoms was associated to decreased anti-rat AChR antibody levels, and differential expression of TGFβ and FoxP3 immunoregulatory transcripts in draining lymph nodes and spleen of treated-EAMG rats. Exposure of rat bone marrow-derived dendritic cells to bifidobacteria or lactobacilli strains upregulated toll-like receptor 2 mRNA expression, a key molecule involved in bacterium recognition via lipotheicoic acid. Live imaging experiments of AChR-specific effector T cells, co-cultured with BMDCs pre-exposed to bifidobacteria, demonstrated increased percentages of motile effector T cells, suggesting a hindered formation of TCR-peptide-MHC complex. Composition of gut microbiota was studied by 16S rRNA gene sequencing, and α and β diversity were determined in probiotic treated EAMG rats, with altered ratios between Tenericutes and Verrucomicrobia (phylum level), and Ruminococcaceae and Lachnospiraceae (family level). Moreover, the relative abundance of Akkermansia genus was found increased compared to healthy and probiotic treated EAMG rats. In conclusion, our findings confirms that the administration of vital bifidobacteria at EAMG onset has beneficial effects on disease progression; this study further supports preclinical research in human MG to evaluate probiotic efficacy as supplementary therapy in MG.
| S-EPMC6951413 | biostudies-literature
Project description:Purpose. This study aimed to determine the dynamic changes of NF-?B-related microRNAs (miRNAs) and cytokines over the course of experimental autoimmune anterior uveitis (EAAU) and elucidate the possible immunopathogenesis. Materials and Methods. Uveitis was induced in Lewis rats using bovine melanin-associated antigen. The inflammatory activity of the anterior chamber was clinically scored, and leukocytes in the aqueous humor were quantified. RNA was extracted from the iris/ciliary bodies and popliteal lymph nodes to reveal the dynamic changes of eight target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and six cytokine mRNAs (IFN-?, IL-17, IL-12A, IL-1?, IL-6, and IL-10). In situ hybridization of miRNA and enzyme-linked immunosorbent assay quantification of cytokines were performed to confirm the results. Results. Disease activity and leukocyte quantification were maximum at day 15 after immunization. The profiling of miRNA revealed downregulation of miR-146a-5p, miR-155-5p, miR-223-3p, and miR-147b and upregulation of miR-182-5p, miR-183-5p, and miR-9-3p. Cytokine analysis revealed IFN-?, IL-17, IL-12A, IL-1?, and IL-6 overexpression, with IL-10 downregulation. Conclusions. Dynamic changes of miRNAs were observed over the course of EAAU. By initiating NF-?B signaling, the expressions of downstream cytokines and effector cells from the Th17 and Th1 lineages were sequentially activated, contributing to the disease.
| S-EPMC4680116 | biostudies-literature