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Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140831 | GEO | 2020/11/13

REPOSITORIES: GEO

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Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders [ftd]

Project description:The role of peripheral inflammation in dementia is an important but complex topic. We present here the largest cohort of peripheral blood gene expression data ever assembled from patients with dementia and matching controls. Importantly, this cohort includes individuals from a diverse set of dementia disorders, including Alzheimer’s Disease (AD), mild cognitive impairment (MCI), and multiple disorders within the frontotemporal dementia (FTD) spectrum. We found strong transcriptional evidence of an innate immune inflammatory response, mediated by monocytes and neutrophils, in AD, MCI, and two FTD subtypes, PSP and nfvPPA. This transcriptional inflammatory response is enriched for genetic risk for AD, in part because it is also enriched for microglial genes, which have previously been implicated in AD risk. Finally, we show that this transcriptional response is strongly enriched for binding of the transcription factors PU.1 and RELA, which have previously been linked to AD risk and progression.

2020-11-13 | GSE140830 | GEO

Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders [ad_mci]

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Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders

Project description:Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders

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Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders [ftd]

Project description:Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders [ftd]

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Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders [ad_mci]

Project description:Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders [ad_mci]

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InnateDB: facilitating systems-level analyses of the mammalian innate immune response.

Project description:Although considerable progress has been made in dissecting the signaling pathways involved in the innate immune response, it is now apparent that this response can no longer be productively thought of in terms of simple linear pathways. InnateDB (www.innatedb.ca) has been developed to facilitate systems-level analyses that will provide better insight into the complex networks of pathways and interactions that govern the innate immune response. InnateDB is a publicly available, manually curated, integrative biology database of the human and mouse molecules, experimentally verified interactions and pathways involved in innate immunity, along with centralized annotation on the broader human and mouse interactomes. To date, more than 3500 innate immunity-relevant interactions have been contextually annotated through the review of 1000 plus publications. Integrated into InnateDB are novel bioinformatics resources, including network visualization software, pathway analysis, orthologous interaction network construction and the ability to overlay user-supplied gene expression data in an intuitively displayed molecular interaction network and pathway context, which will enable biologists without a computational background to explore their data in a more systems-oriented manner.

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Molecular Insights into Innate Immune Response in Captive Koala Peripheral Blood Mononuclear Cells Co-Infected with Multiple Koala Retrovirus Subtypes.

Project description:Koala retrovirus (KoRV) exists in both endogenous and exogenous forms and has appeared as a major threat to koala health and conservation. Currently, there are twelve identified KoRV subtypes: an endogenous subtype (KoRV-A) and eleven exogenous subtypes (KoRV-B to -I, KoRV-K, -L, and -M). However, information about subtype-related immune responses in koalas against multiple KoRV infections is limited. In this study, we investigated KoRV-subtype (A, B, C, D, and F)-related immunophenotypic changes, including CD4, CD8b, IFN-γ, IL-6, and IL-10 mRNA expression, in peripheral blood mononuclear cells (PBMCs) obtained from captive koalas (n = 37) infected with multiple KoRV subtypes (KoRV-A to F) reared in seven Japanese zoos. Based on KoRV subtype infection profiles, no significant difference in CD4 and CD8b mRNA expression was observed in the study populations. Based on the different KoRV subtype infections, we found that the IFN-γ mRNA expression in koala PMBCs differs insignificantly (p = 0.0534). In addition, IL-6 and IL-10 mRNA expression also did not vary significantly in koala PBMCs based on KoRV subtype differences. We also investigated the Toll-like receptors (TLRs) response, including TLR2-10, and TLR13 mRNA in koala PBMCs infected with multiple KoRV subtypes. Significant differential expression of TLR5, 7, 9, 10, and 13 mRNA was observed in the PBMCs from koalas infected with different KoRV subtypes. Therefore, based on the findings of this study, it is assumed that co-infection of multiple KoRV subtypes might modify the host innate immune response, including IFN-γ and TLRs responses. However, to have a more clear understanding regarding the effect of multiple KoRV subtypes on host cytokines and TLR response and pathogenesis, further large-scale studies including the koalas negative for KoRV and koalas infected with other KoRV subtypes (KoRV-A to -I, KoRV-K, -L and -M) are required.

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Enhanced innate type 2 immune response in peripheral blood from patients with asthma.

Project description:BackgroundIn mice, group 2 innate lymphoid cells (ILC2s) likely mediate helminth immunity, inflammation, and tissue repair and remodeling. However, the involvement of ILC2s in human diseases, such as asthma, is not well understood.ObjectivesThe goals of this study were to investigate whether peripheral blood specimens can be used to monitor innate type 2 immunity in human subjects and to examine whether ILC2s are involved in human asthma.MethodsPBMCs from subjects with allergic asthma (AA), subjects with allergic rhinitis (AR), or healthy control (HC) subjects were cultured in vitro with IL-25 or IL-33. Flow cytometry and cell sorting were used to identify, isolate, and quantitate ILC2s in PBMCs.ResultsHuman PBMCs produced IL-5 and IL-13 when stimulated with IL-33 or IL-25 in the presence of IL-2 without antigens. In addition, IL-7 or thymic stromal lymphopoietin were able to replace IL-2. The cell population with phenotypic ILC2 characteristics, lineage(-)CD127(+)CRTH2(+) cells, responded to IL-33 and produced large quantities of IL-5 and IL-13 but undetectable levels of IL-4. PBMCs from subjects with AA produced significantly larger amounts of IL-5 and IL-13 in response to IL-25 or IL-33 than from subjects with AR or HC. The prevalence of ILC2s in blood was greater in the AA group than in the AR group or the HC group.ConclusionsInnate type 2 immune responses are increased in asthma but not in AR, suggesting potential differences in the immunopathogenesis of these diseases. Peripheral blood is useful for evaluating innate type 2 immunity in humans.

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CASP-Model Sepsis Triggers Systemic Innate Immune Responses Revealed by the Systems-Level Signaling Pathways.

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Analysis of cell-specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction.

Project description: Not available

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