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Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE179210 | GEO | 2022/11/02

REPOSITORIES: GEO

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Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [CRISPRscr]

Project description:T helper 2 (TH2) cells play critical roles in protective immunity against parasitic helminth infections and in tissue repair. However, misdirected TH2 cell responses promote allergy and asthma. Using whole-genome CRISPR-Cas9 screens in developing TH2 cells we defined a functional TH2ome for TH2 differentiation and validated a diverse array of molecules not previously linked to TH2 cell development and function. Strikingly, we discovered that integrin avb3 plays a key and previously unappreciated role in the differential polarisation of TH2 cells and their type 2 cytokine expression. Conversely, we did not identify the LFA-1 integrin which mediates inside-out signalling following TCR ligation as part of the T cell synapse and preferentially promotes TH1 differentiation. We find that TH2 cell expression of integrin avb3 is required for the formation of TH2 cell clusters that exhibit enhanced T cell activation, promoting proliferation and TH2 cell differentiation, and thereby potentiating antigen-driven TH2 cell responses.

2022-11-02 | GSE179206 | GEO

Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [RNA-seq I]

2022-11-02 | GSE179207 | GEO

Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation.

Project description:Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation.

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Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [CRISPRscr]

Project description:Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [CRISPRscr]

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Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [RNA-seq I]

Project description:Genome-wide CRISPR screen reveals a key role for integrin avb3 in TH2 cell polarisation [RNA-seq I]

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An avb3 integrin checkpoint is critical for efficient TH2 cytokine polarisation and potentiating antigen-specific immunity [RNA-seq]

Project description:To investigate the role of avb3 integrin in TH2 immunity. We performed gene expression profiling analysis using control vs av-KO TH cells.

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An avb3 integrin checkpoint is critical for efficient TH2 cytokine polarisation and potentiating antigen-specific immunity [ChIP-seq]

Project description:To investigate the role of avb3 integrin in TH2 immunity. We performed gene expression profiling analysis using control vs av-KO TH cells.

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Genome-wide CRISPR screen reveals the synthetic lethality between BCL2L1 inhibition and radiotherapy.

Project description:Radiation therapy (RT) is one of the most commonly used anticancer therapies. However, the landscape of cellular response to irradiation, especially to a single high-dose irradiation, remains largely unknown. In this study, we performed a whole-genome CRISPR loss-of-function screen and revealed temporal inherent and acquired responses to RT. Specifically, we found that loss of the IL1R1 pathway led to cellular resistance to RT. This is in part because of the involvement of radiation-induced IL1R1-dependent transcriptional regulation, which relies on the NF-κB pathway. Moreover, the mitochondrial anti-apoptotic pathway, particularly the BCL2L1 gene, is crucially important for cell survival after radiation. BCL2L1 inhibition combined with RT dramatically impeded tumor growth in several breast cancer cell lines and syngeneic models. Taken together, our results suggest that the combination of an apoptosis inhibitor such as a BCL2L1 inhibitor with RT may represent a promising anticancer strategy for solid cancers including breast cancer.

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Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation.

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