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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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			Action	DRS
	SRR25010558_1.fastq.gz	Fastqsanger.gz
	SRR25010558_2.fastq.gz	Fastqsanger.gz
	SRR25010559_1.fastq.gz	Fastqsanger.gz
	SRR25010559_2.fastq.gz	Fastqsanger.gz
	SRR25010560_1.fastq.gz	Fastqsanger.gz

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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: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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