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Cancer SLC6A6-mediated taurine uptake impairs CD8+ T cell antitumor immunity by upregulating immune checkpoints [mouse RNA-Seq]

ABSTRACT: Cancer SLC6A6-mediated taurine uptake impairs CD8+ T cell antitumor immunity by upregulating immune checkpoints [mouse RNA-Seq]

PROVIDER: PRJNA1048446 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27048917_1.fastq.gz	Fastqsanger.gz
	SRR27048917_2.fastq.gz	Fastqsanger.gz
	SRR27048918_1.fastq.gz	Fastqsanger.gz
	SRR27048918_2.fastq.gz	Fastqsanger.gz
	SRR27048919_1.fastq.gz	Fastqsanger.gz

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Project description:Background: Metabolic dysregulation has been implicated in bronchopulmonary dysplasia development. Taurine is an essential amino acid for neonates and is critically involved in glucose and fatty acid metabolism. Neonatal tissue obtains taurine mainly through the taurine transporter. The biological role of taurine in neonatal lung development has never been explored. As glucose metabolism mechanistically modulates angiogenesis and angiogenesis is the central player for neonatal lung development, we hypothesize that taurine depletion contributes to bronchopulmonary dysplasia development. Results: Although most genes and proteins for oxidative phosphorylation were enriched in hyperoxia pup lungs, the complex-1 activity decreased. The decrease in taurine-dependent complex-1 core subunits, ND5 and ND6, in hyperoxia lungs reasonably explained the discrepancy. Metabolomics analysis demonstrated decreased lung taurine with increased blood taurine of hyperoxia pups, compatible with the decreased taurine transporter expression. Decreased glycosylation and increased degradation explained the decreased taurine transporter expression. The results of the complementary study using tunicamycin and tauroursodeoxycholic acid studies supported that endoplasmic reticulum stress contributes to decreased taurine transporter expression in hyperoxia lungs. The effect of taurine treatment on reducing endoplasmic reticulum stress, increasing ND5 and ND6 expression, angiogenesis, and, most importantly, the alveolar formation is beneficial to hyperoxia rat pups. Conclusion: Hyperoxia exposure causes endoplasmic reticulum stress, increases taurine transporter degradation, and leads to taurine depletion in the neonatal lungs with subsequent metabolic dysregulation, resulting in poor alveolar formation of the neonatal lungs. We provide evidence of the never-being-reported protective role of taurine in neonatal lung development. The fact that taurine attenuates the severity of bronchopulmonary dysplasia by reducing hyperoxia-induced endoplasmic reticulum stress and mitochondrial dysfunction indicates its therapeutic potential for treating bronchopulmonary dysplasia.

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Cancer SLC6A6-mediated taurine uptake impairs CD8+ T cell antitumor immunity by upregulating immune checkpoints [mouse RNA-Seq]

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