Unconventional ST2- and CD127-negative lung ILC2 populations are induced by Alternaria
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ABSTRACT:
PROVIDER: PRJNA561402 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10011531_1.fastq.gz | Fastqsanger.gz | |||
| SRR10011531_2.fastq.gz | Fastqsanger.gz | |||
| SRR10011532_1.fastq.gz | Fastqsanger.gz | |||
| SRR10011532_2.fastq.gz | Fastqsanger.gz | |||
| SRR10011533_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Alternaria exposure is associated with severe asthma in humans. Alternaria exposure in mice potently activates group 2 innate lymphoid cells (ILC2s) via the IL-33/ST2 axis and causes ILC2s to robustly secrete type 2 cytokines. Objective: Our aim was to determine whether conventionally used ILC2 markers, ST2 (IL-33R) and CD127 (IL-7Ra), were sufficient to identify all Th2-cytokine producing ILCs after Alternaria exposure. Methods: Mice received intranasal Alternaria for three days prior to analysis. Lung ILCs were identified by flow cytometry as CD45+Lineage−Thy1.2+ lymphocyte-sized cells, divided into four subsets based on ST2 and CD127 expression, and stained for intracellular cytokines and transcription factors. Sort-purified ILC subpopulations were also analyzed by RNA sequencing and qPCR. Results: Alternaria exposure led to accumulation of all ILC populations regardless of ST2 or CD127 expression. Nearly half of the GATA-3+, IL-5+, and IL-13+ ILCs were “unconventional” as they were either single or double negative for ST2/CD127. Further, these populations upregulated CD25, KLRG1, and ICOS after Alternaria challenge. Some activated unconventional IL-5+ ILC2s also produced IFNγ and IL-17A. In addition to shared ILC2 transcripts (Gata3, Il5, Il13) in all populations, RNA-seq further identified novel transcripts enriched in each subset. Finally, transcripts from all populations that correlated best with IL-5 and IL-13 production included Tnfrsf18, Ffar2, and Pde4b. Conclusions: Unconventional ST2- and CD127-negative mouse lung ILC2 populations are induced by Alternaria. Thus, commonly used lung ILC2 identification methods based on ST2 and CD127 do not accurately account for the total ILC2 burden and may exclude nearly half of these cells.
2019-08-22 | GSE136156 | GEO
Project description:ILC2 cells are a newly described cell type whose biology and contribution to disease are poorly understood. ILC2 cells are activated by allergens, viral infection, and/or epithelial damage via IL-33 and IL-25. ILC2 cells require IL-2, IL-7, IL-25 and IL-33 for their survival and expansion. In mice, ILC2s produce multiple mediators primarily associated with type 2 inflammation (IL-13, IL-5, IL-4, IL-6, IL-9, IL-10, GM-CSF, amphiregulin). ILC2 cells may contribute to the pathology of asthma through multiple mediators that include IL-13-independent pathways. Our goal is to compare transcriptional profiles of IL-33- or IL-25-activated ILC2 cells from blood to characterize these cells and to identify marker(s) that can be utilized to detect them in human tissue. ILC2 cells (Lineage negative, CRTH2+, CD161+, CD127+) were purified from human blood of 5 different donors by flow cytometry. The ILC2 yield ranged from 20,000 to 165,000 cells per donor (0.001-0.008% WBC). Purified ILC2s were expanded in vitro in the presence of IL-2, IL-7, IL-33 and IL-25 (each at 50 ng/ml) for 7-10 days. Expanded cells maintained the ILC2 phenotype (Lineage negative, CRTH2+, CD161+, CD127+). The cells were rested for 2 days in the presence of 1 ng/ml IL-2 and IL-7 and then treated in the presence of 1 ng/ml IL-2 and IL-7 with either media control, IL-25 (50 ng/ml), IL-33 (50 ng/ml), and/or TSLP (50 ng/ml) in combination, for 6 or 24 hours. Whole RNA was isolated via the RNeasy kit (Qiagen). Stratagene Universal Human Reference RNA was used as the reference.
2013-12-31 | E-GEOD-45458 | biostudies-arrayexpress
Project description:Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens – including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals, but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 were found to be uniquely pre-primed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine producing capacity of ILC2. Moreover, amino acid determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
2022-12-22 | PXD038792 | Pride
Project description:Foxp3+ regulatory T cells (Tregs) are critical mediators of peripheral tolerance and immune homeostasis. Tregs that express the IL-33 receptor ST2 are enriched in peripheral nonlymphoid tissues and can exert a variety of tissue-specific functions from metabolic regulation within adipose tissue to skeletal muscle repair. However, the relationship between ST2+ and ST2- Tregs within and across different tissues remains unclear. To compare murine ST2- and ST2+ Tregs within and across tissues, we performed RNA sequencing (RNAseq) of ST2-CD44hi and ST2+CD44hi Tregs from blood, spleen, lungs, visceral adipose tissue (VAT), colon, and skin. RNAseq was also performed on ST2- CD44lo CD62L+ Tregs from the spleen and lungs. We found that the tissue microenvironment was the major factor shaping the transcriptome of Tregs across tissues. Across the tissues studied, Treg transcriptomes displayed an ordered hierarchy that may represent graded levels of activation or differentiation across tissues. We also identified a core signature that distinguished ST2+ Tregs from ST2- Tregs across tissues and a large number of differentially expressed genes between ST2- and ST2+ Tregs within individual tissues that could support the tissue-specific adaptation and function of ST2+ Tregs. In summary, our work highlights the unique, tissue-specific phenotype of ST2+ Tregs and reveals a core ST2+ Treg transcriptional signature shared across tissues.
2022-07-24 | GSE182322 | GEO
Project description:Colorectal cancer (CRC) was induced in Foxp3/eGFP reporter mice by the azoxymethane/dextran sulphate sodium salt (AOM/DSS) protocol. Mice were injected i.p. with the procarcinogen AOM (12.5 mg/kg of body weight). After 1 week, mice received drinking water supplemented with 2.5% DSS for 5 to 7 days, followed by 2 weeks of regular water. The DSS administration was repeated twice with 2% DSS. Mice were sacrificed at week 11 and lamina propia lymphocytes (LPLs) from the colon were isolated. CD4+FOXP3+ (eGFP+) ST2+ or ST2- Tregs were separated from colonic LPLs of CRC induced mice using a FACSAria II cell sorter. Microarray analysis was performed to analyze if ST2+ FOXP3+ Tregs from the colon of CRC mice present a distinct transcription pattern compared to ST2- FOXP3+ Tregs. By this, the role of ST2 for Treg function during intestinal tumorigenesis should be characterized.
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2018-03-15 | GSE111901 | GEO
Project description:The ETS1 transcription factor is required for the development and cytokine-induced expansion of ILC2 ILC2 cells isolated from ETS1-deleted or litter mate control mice were cultured on OP9-DL1 with IL-7 and IL-33. Subsequently, RNA from ICOS+ cells was extracted, labelled and hybridized to Affymetrix microarrays. The goal of this study is to investigate ETS1-dependent genes in developing ILC2 cells.
2016-04-01 | E-GEOD-79742 | biostudies-arrayexpress
Project description:We describe the effects of Treg ST2 expression on muscle regeneration. We compare regneration from cryo-injured tibialis anterior muscle from Foxp3-Cre/ST2-flox vs Foxp3-Cre mice 8 days post-injury. These analyses from whole muscle provide insight into the role of muscle Tregs in the context of regeneration. The tibialis anterior muscle from male Foxp3-Cre/ST2 flox or Foxp3-Cre/ST2 WT C57BL/6 mice (2 months old) were cryo-injured using a liquid nitrogen chilled metal probe for 8 seconds. 8 days post-injury whole muscle was harvested and snap frozen in liquid nitrogen. Whole muscle was then homogenized directly in TriZol and gene expression profiling was performed on Affymetrix Mouse Gene 1.0 ST Arrays.
2016-01-10 | E-GEOD-76697 | biostudies-arrayexpress
Project description:Type 2 innate lymphoid cells (ILC2s) play a pivotal role in type 2 asthma. CD226 is a costimulatory molecule involved in various inflammatory diseases. Here, we aimed to investigate CD226 expression and function within human and mouse ILC2s, and to assess the impact of targeting CD226 on ILC2-mediated airway hyperreactivity (AHR). Our findings demonstrated an inducible expression of CD226 in activated ILC2s, enhancing their cytokine secretion and effector functions. Blocking CD226 ameliorates ILC2-dependent AHR in IL-33 and Alternaria Alternata-induced models. Interestingly, CD226 is expressed and inducible in human ILC2s, and its blocking reduces cytokine production. Finally, we showed that peripheral ILC2s in asthmatic patients exhibited elevated CD226 expression compared to healthy controls.Our findings underscore the potential of CD226 as a novel therapeutic target in ILC2s, presenting a promising avenue for ameliorating AHR and allergic asthma.
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