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Autoimmunity and infection give rise to distict inflammatory Th17 subsets [single-cell RNA-seq]

ABSTRACT: Autoimmunity and infection give rise to distict inflammatory Th17 subsets [single-cell RNA-seq]

PROVIDER: PRJNA982101 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24888155.fastq.gz	Fastqsanger.gz
	SRR24888156.fastq.gz	Fastqsanger.gz
	SRR24888157.fastq.gz	Fastqsanger.gz
	SRR24888158.fastq.gz	Fastqsanger.gz
	SRR24888159.fastq.gz	Fastqsanger.gz

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Autoimmunity and infection give rise to distict inflammatory Th17 subsets

Project description:Autoimmunity and infection give rise to distict inflammatory Th17 subsets

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Autoimmunity and infection give rise to distict inflammatory Th17 subsets [bulk RNA-seq]

Project description:Autoimmunity and infection give rise to distict inflammatory Th17 subsets [bulk RNA-seq]

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Autoimmunity and infection give rise to distict inflammatory Th17 subsets [bulk RNA-seq]

Project description:Th17 cells are a heterogeneous population that is critical for tissue homeostasis and inflammation during clearance of infections and autoimmunity. Despite substantial efforts distinguishing homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells is poorly understood. In this study, we show that the inflammatory Th17 engaged in autoimmune colitis and those involved in infection-induced colitis are two distinguishable populations illustrated by their distinct responses to a pharmacological molecule, clofazimine (CLF). Distinct from existing Th17 inhibitors, CLF selectively inhibits pro-autoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells through restricting Aldh1l2expression. Using bulk RNA sequencing, we explored transcriptional response to CLF on in vitro differentiated inflammatory and homeostatic Th17 cells. Notably, we identified a unique suppression in the transcription of signature inflammatory genes in Th17 cells with a marginal effect on those elicited by infection.

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Autoimmunity and infection give rise to distict inflammatory Th17 subsets [single-cell RNA-seq]

Project description:Th17 cells are a heterogeneous population that is critical for tissue homeostasis and inflammation during clearance of infections and autoimmunity. Despite substantial efforts distinguishing homeostatic and inflammatory roles of Th17 cells, the mechanism underlying the divergent functions of inflammatory Th17 cells is poorly understood. In this study, we show that the inflammatory Th17 engaged in autoimmune colitis and those involved in infection-induced colitis are two distinguishable populations illustrated by their distinct responses to a pharmacological molecule, clofazimine (CLF). Distinct from existing Th17 inhibitors, CLF selectively inhibits pro-autoimmune Th17 cells while preserving the functional state of infection-elicited Th17 cells through restricting Aldh1l2expression. Using single-cell RNA sequencing, we explored inflammatory Th17 transcriptional response to CLF from the colonic tissue of mice during autoimmune colitis and Citrobacter rodentiuminfection using Rorc gfp/+ reportor mice. Notably, we identified a unique suppression in the transcription of signature inflammatory genes in Th17 cells from autoimmune colitis with a marginal effect on those elicited by infection. Additionally, we illustrate with these data that the transcriptionally programming of pro-autoimmune Th17 cells are, indeed, unique compared to infection-elicited Th17 cells. Finally, we analyzed the impact of CLF on human inflammatory Th17 cells from the inflammed colon of a patient with IBD.

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Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Project description:Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

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Autoimmunity and infection give rise to distict inflammatory Th17 subsets

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

2023-06-13 | GSE234594 | GEO

Human hepatocytes can give rise to intrahepatic cholangiocarcinomas

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Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity.

Project description:While intestinal Th17 cells are critical for maintaining tissue homeostasis, recent studies have implicated their roles in the development of extra-intestinal autoimmune diseases including multiple sclerosis. However, the mechanisms by which tissue Th17 cells mediate these dichotomous functions remain unknown. Here, we characterized the heterogeneity, plasticity, and migratory phenotypes of tissue Th17 cells in vivo by combined fate mapping with profiling of the transcriptomes and TCR clonotypes of over 84,000 Th17 cells at homeostasis and during CNS autoimmune inflammation. Inter- and intra-organ single-cell analyses revealed a homeostatic, stem-like TCF1+ IL-17+ SLAMF6+ population that traffics to the intestine where it is maintained by the microbiota, providing a ready reservoir for the IL-23-driven generation of encephalitogenic GM-CSF+ IFN-γ+ CXCR6+ T cells. Our study defines a direct in vivo relationship between IL-17+ non-pathogenic and GM-CSF+ and IFN-γ+ pathogenic Th17 populations and provides a mechanism by which homeostatic intestinal Th17 cells direct extra-intestinal autoimmune disease.

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Project description:Effector TH17 cells give rise to long-lived TRM cells that are essential for an immediate response against bacterial infection

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