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

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

PROVIDER: PRJNA896639 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22133997.fastq.gz	Fastqsanger.gz
	SRR22133998.fastq.gz	Fastqsanger.gz

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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.

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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]

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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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Integrin a5, aV, and aVb3 in zebrafish embryos at the 12 somite stage

Project description:Integrins are a major class of heterodimeric adhesion receptors composed of an a and b subunit that mediate cell adhesion to the extracellular matrix (ECM). The extracellular matrix protein fibronectin is important for early vertebrate development, and Integrin a5b1 and aVb3 are the two primary fibronectin receptors. To better define the integrin – ECM protein network at 10-13 somite stage of zebrafish development, we performed co-immunoprecipitation and Mass Spectrometry (MS) based proteomics using FLAG-tagged Integrin a5, aV, and aVb3 expressed in maternal zygotic a5 mutant (MZa5-/-) embryos. We found that Integrin a5b1 and aVb1 are the functional fibronectin receptors, whereas Integrin aVb3 displayed low affinity to both fibronectins (Fn1a and Fn1b). In addition, basement membrane ligands Laminins (lama1, lamb1a, lamc1) are roughly equal in all three datasets while Thrombospondins (thbs3b, thbs4b) and cartilage oligomeric matrix protein (comp/thbs5) are found exclusively in the aV dataset. Our results suggest a diverse role of aV class integrins in ECM protein recruitment.

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