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TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha

ABSTRACT: TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha

PROVIDER: PRJNA788273 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17208813.fastq.gz	Fastqsanger.gz
	SRR17208814.fastq.gz	Fastqsanger.gz
	SRR17208815.fastq.gz	Fastqsanger.gz
	SRR17208816.fastq.gz	Fastqsanger.gz
	SRR17208817.fastq.gz	Fastqsanger.gz

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TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [ultradeep]

Project description:Type 1 diabetes (T1D) is an autoimmune disease that results in the destruction of insulin producing pancreatic b-cells. One of the genes associated with T1D is TYK2, which encodes a Janus kinase with critical roles in type-I interferon (IFN) mediated intracellular signalling. To study the role of TYK2 in human pancreatic b-cell development and response to IFNa, we generated TYK2 knockout human iPSCs and directed them into the pancreatic endocrine lineage. Unexpectedly, loss of TYK2 compromised the emergence of endocrine precursors by regulating KRAS expression, however, mature b-cell function was not affected. In the mature stem cell-derived islets, the loss or inhibition of TYK2 prevented IFNa-induced antigen processing and presentation, including MHC Class I expression, enhancing their survival against T-cell cytotoxicity. These results identify an unsuspected role for TYK2 on b-cell development and support TYK2 inhibition in adult b-cells as a potent therapeutic target to halt T1D progression.

2022-09-19 | GSE190727 | GEO

TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [tyk2_scRNAseq]

2022-09-19 | GSE190726 | GEO

TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [tyk2_bulkseq]

2022-09-19 | GSE190725 | GEO

TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [tyk2_bulkseq]

Project description:TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [tyk2_bulkseq]

| PRJNA788276 | ENA

TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [tyk2_scRNAseq]

Project description:TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [tyk2_scRNAseq]

| PRJNA788275 | ENA

TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [ultradeep]

Project description:TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha [ultradeep]

| PRJNA788277 | ENA

Transcriptome analysis reveals a major impact of Tyk2 on the expression of interferon responsive and metabolic genes

Project description:Peritoneal macrophages of Tyk2-/- and wildtype (wt) mice were compared before and after six hours of LPS treatment. Interferon responsive genes are lower expressed in Tyk2-/- macrophages at the basal level, metabolic genes higher before, but even more after LPS treatment. cDNA from macrophages from three replicates of three Tyk2-/- and three wt mice before and after six hours of LPS treatment, respectively, was hybridized to a microarray and analyzed.

2010-04-01 | E-GEOD-19733 | biostudies-arrayexpress

Comparison of the expression profiles of wild-type (WT), Tyk2-deficient (Tyk2-/-) and kinase-inactive Tyk2 mutant (Tyk2K923E) NK cells

Project description:Define the impact of Tyk2 and Tyk2K923E on the transcriptome of NK cells Tyrosine kinase 2 (TYK2) is a Janus kinase (JAK) that is crucially involved in inflammation, carcinogenesis and defense against infection. The cytotoxic activity of natural killer (NK) cells in TYK2-deficient (Tyk2-/- ) mice is severely reduced, although the underlying mechanisms are largely unknown. Using Tyk2-/- mice and mice expressing a kinase-inactive version of TYK2 (Tyk2K923E), we show that NK cell function is partly independent of the enzymatic activity of TYK2. Tyk2-/- and Tyk2K923E NK cells develop normally in the bone marrow, but the maturation of splenic Tyk2-/- NK cells (and to a lesser extent of Tyk2K923E NK cells) is impaired. In contrast, the production of interferon ? (IFN?) in response to interleukin 12 (IL-12) or to stimulation through NK cell-activating receptors strictly depends on the presence of enzymatically active TYK2. The cytotoxic activity of Tyk2K923E NK cells against a range of target cells in vitro is higher than that of Tyk2-/- NK cells. Consistently, Tyk2K923E mice control the growth of NK cell-targeted tumors significantly better than TYK2-deficient mice, showing the physiological relevance of the finding. Inhibitors of TYK2’s kinase activity are being developed for the treatment of inflammatory diseases and cancers, but their effects on tumor immune surveillance have not been investigated. Our finding that TYK2 has kinase-independent functions in vivo suggests that such inhibitors will leave NK cell mediated tumor surveillance largely intact and that they will be suitable for use in cancer therapy. Splenic NK cells derived from WT, Tyk2-/- and Tyk2K923E mice (DX5-MACS enriched from 3-4 mice per genotype) were grown in the presence rhIL-2 (5000 U/ml) for 7 days. Three independent expreiments (= biological replicates)

2015-04-28 | E-GEOD-68294 | biostudies-arrayexpress

Transcriptome analysis reveals a major impact of Tyk2 on the expression of interferon responsive and metabolic genes

2010-04-01 | GSE19733 | GEO

TYK2 regulates human pancreatic beta-cell development and its responses to interferon-alpha

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-09-19 | GSE190728 | GEO