ICOS-driven Cholesterol and Cortisol Biosynthesis Shape IL-10 Production in ILC2s to Regulate Airway Hyperreactivity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1219118 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR32230358_1.fastq.gz | Fastqsanger.gz | |||
| SRR32230358_2.fastq.gz | Fastqsanger.gz | |||
| SRR32230360_1.fastq.gz | Fastqsanger.gz | |||
| SRR32230360_2.fastq.gz | Fastqsanger.gz |
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Project description:Group 2 innate lymphoid cells (ILC2) induce type 2 inflammation in the lungs in response to allergens. Here, we investigated the regulatory mechanism of IL-10 production by ILC2s on the development of airway hyperreactivity (AHR), with a particular focus on the role of ICOS. Our findings demonstrate that inhibition of ICOS in pulmonary ILC2s significantly promotes IL-10 production. Lack of ICOS reprograms ILC2 steroid metabolism, resulting in increased cholesterol and cortisol biosynthesis and Glucocorticoid receptor (GR) activation. Consequently, this reprogramming regulates MAF and NFIL3 activation, thereby promoting IL-10 production. We notably found that in vivo GR inhibition or ILC2-specific GR deficiency exacerbated the development of AHR in multiple mouse models. Finally, we extended our findings to a human setting and demonstrated concordant results between murine models and human ILC2s. Taken together, our results therefore indicate that ICOS negatively regulates IL-10 production in ILC2s by controlling cholesterol and cortisol biosynthesis.
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Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
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Project description:Mechanosensitive ion channels sense force and pressure in immune cells to drive the inflammatory response in highly mechanical organs. Here we report that Piezo1 channels repress group 2 innate lymphoid cells (ILC2s)-driven type 2 inflammation in the lungs. Piezo1 is induced on lung ILC2s upon activation, as genetic ablation of Piezo1 in ILC2s increases their function and exacerbates the development of airway hyperreactivity (AHR). Conversely, Piezo1 agonist Yoda1 reduces ILC2-driven lung inflammation. Mechanistically, Yoda1 inhibits ILC2 cytokine secretion and proliferation in a KLF2-dependent manner, as we further found that Piezo1 engagement reduces ILC2 oxidative metabolism. Consequently, in vivo Yoda1 treatment notably reduces the development of AHR in experimental models of ILC2-driven allergic asthma. Human circulating ILC2s express and induce Piezo1 upon activation, as Yoda1 treatment of humanized mice reduces human ILC2-driven AHR. Our studies define Piezo1 as a critical regulator of ILC2s and we propose the potential of Piezo1 activation as a novel therapeutic approach for the treatment of ILC2-driven allergic asthma.
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2016-06-30 | E-GEOD-81700 | biostudies-arrayexpress
Project description:ICOS (Inducible Costimulator) is a T cell costimulatory molecule. We found that the cloned T-cell hybridoma 6-13-64 consists of two populations, ICOS expressing and non-expressing. The aim of this study is to screen for candidate genes that regulate ICOS gene expression by transcriptional profiling and comparison of the ICOS-positive and ICOS-negative subpopulations isolated from the 6-13-64 T-cell hybridoma. One-condition experiment, ICOS(-) vs. ICOS(+) cells. Independently grown and harvested. One replicate per array.
2012-03-31 | E-GEOD-20922 | biostudies-arrayexpress
Project description:ICOS (Inducible Costimulator) is a T cell costimulatory molecule. We found that the cloned T-cell hybridoma 6-13-64 consists of two populations, ICOS expressing and non-expressing. The aim of this study is to screen for candidate genes that regulate ICOS gene expression by transcriptional profiling and comparison of the ICOS-positive and ICOS-negative subpopulations isolated from the 6-13-64 T-cell hybridoma.
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