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Transcriptomic profile of Tfh cells during intestinal helminth infection

ABSTRACT: Transcriptomic profile of Tfh cells during intestinal helminth infection

PROVIDER: PRJNA771666 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16355747_1.fastq.gz	Fastqsanger.gz
	SRR16355747_2.fastq.gz	Fastqsanger.gz
	SRR16355748_1.fastq.gz	Fastqsanger.gz
	SRR16355748_2.fastq.gz	Fastqsanger.gz
	SRR16355749.fastq.gz	Fastqsanger.gz

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Transcriptomic profile of Tfh cells during intestinal helminth infection

Project description:The goal of this study was to define the regulation of Tfh cell response during intestinal helminth infection. Using the helminth Trichuris muris, we performed RNA-seq analysis on Tfh cells that develop during acute vs chronic helminth infection. We found that the transcriptomic profile of acute vs chronic induced Tfh cells are distinct and they express Th2/Th1-associated genes, respectively.

2021-10-20 | GSE185992 | GEO

Chromatin accessibility profile of Tfh cells during intestinal helminth infection

Project description:The goal of this study was to define the regulation of Tfh cell response during intestinal helminth infection. Using the helminth Trichuris muris, we performed ATAC-seq analysis on Tfh cells that develop during acute vs chronic helminth infection. We found that the epigenetic profile of acute vs chronic induced Tfh cells are distinct by adopting Th2 and Th1 cell phenotypes, respectively. For example, Th2-associated genes such as the Il4 locus was more accessible in acute-induced Tfh cells (and vice versa for Th1-associated genes in chronic-induced Tfh cells).

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Chromatin accessibility profile of Tfh cells during intestinal helminth infection

Project description:Chromatin accessibility profile of Tfh cells during intestinal helminth infection

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Hypoxia-inducible factor 2α promotes protective Th2 cell responses during intestinal helminth infection

Project description:Th2 cells must sense and adapt to the tissue milieu in order to provide protective host immunity and tissue repair. Here, we examined the mechanisms promoting Th2 cell differentiation and function within the small intestinal lamina propria. Single cell RNA-seq analyses of CD4+ T cells from the small intestinal lamina propria of helminth infected mice revealed high expression of the gene Epas1, encoding the transcription factor hypoxia-inducible factor 2a (HIF2α). In vitro, exposure to hypoxia or genetic HIF2α activation promoted Th2 cell differentiation, even under non-polarizing conditions. In mice, HIF2α activation in CD4+ T cells promoted intestinal Th2 cell accumulation in the absence of infection, and HIF2α-deficiency impaired CD4+ T cell-mediated host immunity to intestinal helminth infection. Our findings identified hypoxia, and the oxygen-regulated transcription factor Hypoxia-Inducible Factor 2α (HIF2α), as key regulators of Th2 cell differentiation and function within the small intestine.

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Notch-activated basophils support intestinal CD4+ T cell fate and function during helminth infection

Project description:Helminth infections affect billions of people worldwide and cause substantial morbidity. Intestinal helminth infection provokes Type 2 inflammation orchestrated by CD4+ T helper 2 (Th2) cells. Th2s produce interleukin (IL)-4 and IL-13 that prompt an epithelial “weep and sweep” response to drive parasite clearance. Tissue-specific cues optimize CD4+ T cell responses, but the mechanisms regulating intestinal Th2 responses remain unclear. Previously, we identified that the Notch signaling pathway in basophils, rare granulocytes, drove effective parasite clearance and an optimal Th2 response during Trichurismuris infection, a mouse model of human whipworm. Here we report basophil-intrinsic Notch was required for infection-elicited Th2 cytokine responses and a broader IL-4 production program across intestinal CD4+ T cell subsets. In vitro, basophils supported CD4+ T cell cytokine production in a contact-dependent manner, independent of basophil-secreted factors, and was dependent on autocrine IL-4 production from CD4+ T cells. In vivo, basophil-intrinsic Notch mediated basophil-Th2 cell interactions in the cecum during infection. Thus, Notch-programmed basophils act in a contact-dependent manner to optimize intestinal CD4+ T cell function during helminth infection. These findings improve our understanding of the tissue-specific mechanisms regulating intestinal CD4+ T cell responses at inflamed mucosal barriers during Type 2 immunity.

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Hypoxia-inducible factor 2α promotes protective Th2 cell responses during intestinal helminth infection [RNA-seq]

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Global gene expression profile of PD1+ Tfh cells, CD62L+ Tfh cells, non-Tfh effector cells

Project description:Global gene expression profile of PD1+ Tfh cells, CD62L+ Tfh cells, non-Tfh effector cells

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Project description:Intestinal helminth skews dendritic cell development to counter the anti-helminth immune response

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Project description:Differential gene expression profile of Tfh and non-Tfh cells from both Wt and miR-155-/- mice spleens.

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