Th2 single-cell heterogeneity and clonal interorgan distribution in helminth-infected mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA751603 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15327853.fastq.gz | Fastqsanger.gz | |||
| SRR15327854.fastq.gz | Fastqsanger.gz | |||
| SRR15327855.fastq.gz | Fastqsanger.gz | |||
| SRR15327856.fastq.gz | Fastqsanger.gz | |||
| SRR15327857.fastq.gz | Fastqsanger.gz |
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Project description:Th2 cells provide effector functions in type 2 immune responses to helminths and allergens. Despite substantial knowledge about molecular mechanisms of Th2 cell differentiation, there is little information on Th2 cell heterogeneity and clonal distribution between organs mainly due to technical limitations. To address this issue, we performed combined single-cell transcriptome and TCR clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLN) and lung after infection with Nippostrongylus brasiliensis (Nb) as a model of human hookworm infection. We identified strong organ-specific expression profiles, but also found populations with conserved effector or migration signatures. A substantial MLN subpopulation with an interferon response signature suggests a role for interferon-signaling in Th2 cell differentiation or diversification. RNA-inferred developmental directions further implied proliferation as a hub for differentiation decisions. Although the TCR repertoire appeared to be highly heterogeneous, we identified expanded Th2 clones and CDR3 motifs. Clonal relatedness between distant organs confirmed the effective exchange of Th2 effector cells. However, locally expanded clones dominated the response, as the most expanded clones in MLN and lung did not overlap. This new insight in Th2 cell subsets and clonal relatedness in distant organs demonstrates their heterogeneity and suggests that they serve distinct effector functions.
2022-08-19 | GSE181342 | GEO
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.
2025-04-01 | GSE288268 | GEO
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.
2025-04-01 | GSE288269 | GEO
Project description:Th2 cells provide effector functions in type 2 immune responses to helminths and allergens. Despite knowledge about molecular mechanisms of Th2 cell differentiation, there is little information on Th2 cell heterogeneity and clonal distribution between organs. To address this, we performed combined single-cell transcriptome and T-cell receptor (TCR) clonotype analysis on murine Th2 cells in mesenteric lymph nodes (MLNs) and lung after infection with Nippostrongylus brasiliensis (Nb) as a human hookworm infection model. We find organ-specific expression profiles, but also populations with conserved migration or effector/resident memory signatures that unexpectedly cluster with potentially regulatory Il10posFoxp3neg cells. A substantial MLN subpopulation with an interferon response signature suggests a role for interferon signaling in Th2 differentiation or diversification. Further RNA-inferred developmental directions indicate proliferation as a hub for differentiation decisions. Although the TCR repertoire is highly heterogeneous, we identified expanded clones and CDR3 motifs. Clonal relatedness between distant organs confirmed effective exchange of Th2 effector cells, although locally expanded clones dominated the response. We further cloned an Nb-specific TCR from an expanded clone in the lung effector cluster and describe surface markers that distinguish transcriptionally defined clusters. These results provide insights in Th2 cell subset diversity and clonal relatedness in distant organs.
| S-EPMC9391044 | biostudies-literature
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).
2021-10-20 | GSE186062 | GEO
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
Project description:CD4+T cells are differentiated into Th1, Th2, Th17 and Treg cells after Antigen presentation by other cell types such as dendritic cells, macrophages and B cells in Lymph nodes. Those differentiated CD4+T cells are subdivided into cell subsets by their producing cytokines and surface markers. We recently identified that ST2 expressing Th2 cells highly produced IL-5 comparing to ST2- Th2 cells in helminth infection. In this study, we investigated the RNAseq analysis to characterize these Th2 cells.
2018-09-20 | GSE120173 | GEO
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.
2025-08-27 | GSE297084 | GEO
Project description:Hypoxia-inducible factor 2α promotes protective Th2 cell responses during intestinal helminth infection.
| PRJNA1216650 | ENA
Project description:Hypoxia-inducible factor 2α promotes protective Th2 cell responses during intestinal helminth infection
| PRJNA1216654 | ENA