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Free cholesterol primes the IFN-I response by facilitating the release of TLR9 from UNC93B1

ABSTRACT: Free cholesterol primes the IFN-I response by facilitating the release of TLR9 from UNC93B1

PROVIDER: PRJNA1067108 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27667423_1.fastq.gz	Fastqsanger.gz
	SRR27667423_2.fastq.gz	Fastqsanger.gz
	SRR27667424_1.fastq.gz	Fastqsanger.gz
	SRR27667424_2.fastq.gz	Fastqsanger.gz
	SRR27667425_1.fastq.gz	Fastqsanger.gz

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Free cholesterol primes the IFN-I response by facilitating the release of TLR9 from UNC93B1

Project description:Elevated cholesterol is positively associated with autoimmunity. However, it is unclear which mechanism directly link them. Here, we report that free cholesterol in the endolysosomal membrane regulates the IFN-I response in plasmacytoid dendritic cells (pDCs) by facilitating the release of TLR9 from UNC93B1. The cholesterol transporter NPC1 was highly expressed in pDCs, and conditional deletion of Npc1 via Cd11c-Cre (Npc1∆DC) impaired IFNα production by TLR9-stimulated pDCs. Npc1∆DC mice exhibited a weakened IFNα response to HSV-1 infection, and ameliorated anti-DNA autoantibodies and nephritis when crossed to B6.Sle1yaa transgenic lupus model. Mechanistically, through click chemistry-based proteome-wide screening, we found that the TLR chaperone UNC93B1 could bind to free cholesterol. The juxtamembrane cholesterol gradient, mediated by NPC1, promoted TLR9 release from UNC93B1. Increased membrane-bound cholesterol dramatically enhanced IFNα response by murine and human pDCs. Our results suggested that the participation of free cholesterol in TLR9 signaling could directly link elevated cholesterol with autoimmunity.

2025-01-18 | GSE253771 | GEO

Free cholesterol primes the IFN-I response

Project description:we report that free cholesterol in the endolysosomal membrane regulates the IFN-I response in plasmacytoid dendritic cells (pDCs) by facilitating the release of TLR9 from UNC93B1.

2024-04-29 | PXD051868 |

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Tlr9

Project description:Rattus norvegicus Tlr9, toll-like receptor 9 [Source:RGD Symbol;Acc:631352], is expressed in 4 baseline experiment(s);

| ENSRNOG00000048161 | ExpressionAtlas

Tlr9

Project description:Rattus norvegicus Tlr9, toll-like receptor 9 [Source:RGD Symbol;Acc:631352], is differentially expressed in 1 experiment(s);

| ENSRNOG00000048161 | ExpressionAtlas

TLR9

Project description:Homo sapiens TLR9, toll like receptor 9 [Source:HGNC Symbol;Acc:HGNC:15633], is differentially expressed in 5 experiment(s);

| ENSG00000239732 | ExpressionAtlas

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Project description:Homo sapiens TLR9, toll like receptor 9 [Source:HGNC Symbol;Acc:HGNC:15633], is expressed in 10 baseline experiment(s);

| ENSG00000239732 | ExpressionAtlas

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Project description:Mus musculus Tlr9, toll-like receptor 9 [Source:MGI Symbol;Acc:MGI:1932389], is differentially expressed in 58 experiment(s);

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