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Interferons are the key cytokines acting on pancreatic islets in type 1 diabetes

ABSTRACT: Interferons are the key cytokines acting on pancreatic islets in type 1 diabetes

PROVIDER: PRJNA986896 | ENA |

REPOSITORIES: ENA

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Interferons are the key cytokines acting on pancreatic islets in type 1 diabetes

Project description:The pro-inflammatory cytokines IFNα, IFNγ, IL-1β and TNFα may contribute to innate and adaptive immune responses during islet inflammation (insulitis) in type 1 diabetes (T1D). We used deep RNA-sequencing analysis to characterize the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by T1D. IFNα and IFNγ had a much greater impact on the beta cell transcriptome when compared to IL-1β and TNFα. The IFN-induced gene signatures have a strong correlation with those observed in beta cells from T1D patients, and the level of expression of specific IFN-stimulated genes is positively correlated with proteins present in islets of these individuals, regulating beta cell responses to “danger signals” such as viral infections. These data suggest that IFNα and IFNγ are the central cytokines at the islet level in T1D, contributing to the triggering and amplification of autoimmunity.

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Project description:ImmGen Cytokines: Interferons

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Human islets exposed to cytokines IL-1β and IFN-γ

Project description:In the context of T1 Diabetes, pro-inflammatory cytokines IL-1β and IFN-γ are known to contribute to β-cell apoptosis; The measurement of mRNA expression following β-cell exposure to these cytokines gives a picture of the changes in gene expression characterizing the path to β-cell dysfunction and death. Human islets were isolated and exposed (or not) to IL-1β and IFN-γ. The samples were collected at various time points for profiling with Affymetrix arrays. These measurements were performed three times.

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Identifying metabolite changes in human islets treated with Phospho-BAD mimicry and Inflammatory cytokines

Project description:The goal of this study was to associate metabolite changes with protection of human islets from cell death induced by the diabetogenic stress of inflammatory cytokines. Protection of human islet viability was accomplished via enhanced glucose metabolism using phospho-BAD mimicry peptide treatment.

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Eutherian interferons

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Influence of type I Interferons on function of splenic conventional dendritic cells.

Project description:Type I Interferons encompasses a large family of closely related cytokines comprising of at least 13 IFN-α isotypes and single IFN-β. Both IFN-α and IFN-β exert their activity through a common receptor IFNAR. Type I Interferons have broad regulatory effects and various subtypes of dendritic cells are influenced by this cytokines. In our study we asked question whether the low, constitutive levels of type I Interferons produced under steady state conditions are important for proper function of splenic conventional dendritic cells. In this approach we sorted out two populations (CD8α+ and CD8α-) of splenic dendritic cells (DCs) from untreated WT, IFN-β-/- and IFNAR-/- C57Bl/6 mice. All mice were between 8-10 weeks old. Further we isolated RNA and performed microarray analysis. Each DCs population was repeated twice.

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The human pancreatic islet transcriptome: impact of pro-inflammatory cytokines

Project description:We have used RNA-seq to identify transcripts, including splice variants, expressed in human islets of Langerhans under control condition or following exposure to the pro-inflammatory cytokines interleukin-1β (IL-1β) and interferon-γ (IFN-γ). A total of 29,776 transcripts were identified as expressed in human islets. Expression of around 20% of these transcripts was modified by pro-inflammatory cytokines, including apoptosis- and inflammation-related genes. Chemokines were among the transcripts most modified by cytokines. Interestingly, 35% of the genes expressed in human islets undergo alternative splicing as annotated in RefSeq, and cytokines caused substantial changes in spliced transcripts. Nova1, previously considered a brain-specific regulator of mRNA splicing, is expressed in islets. 25/41 of the candidate genes for type 1 diabetes are expressed in islets, and cytokines modified expression of several of these transcripts. 5 human islet of Langerhans preparations examined under 2 conditions (control and cytokine treatment)

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Single-cell RNA-sequencing of mouse islets exposed to proinflammatory cytokines [18hrs]

Project description:Single-cell RNA-sequencing of mouse islets exposed to proinflammatory cytokines [18hrs]

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Influence of type I Interferons on function of splenic conventional dendritic cells.

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