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Transcriptomic profiling of the role of Ctla4 in the innate immune system

ABSTRACT: Transcriptomic profiling of the role of Ctla4 in the innate immune system

PROVIDER: PRJNA1069073 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27731675_1.fastq.gz	Fastqsanger.gz
	SRR27731675_2.fastq.gz	Fastqsanger.gz
	SRR27731676_1.fastq.gz	Fastqsanger.gz
	SRR27731676_2.fastq.gz	Fastqsanger.gz
	SRR27731677_1.fastq.gz	Fastqsanger.gz

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Transcriptomic profiling of the role of Ctla4 in the innate immune system

Project description:The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface of the gut microbiome and mucosal immunity, adaptive and innate lymphoid populations regulate the balance between commensal micro-organisms and pathogens. Checkpoint inhibitors (CPI), particularly those targeting the CTLA-4 pathway, disrupt this fine balance and can lead to inflammatory bowel disease (IBD) and immune checkpoint colitis (CPI-C). Here, we show that CTLA-4 is expressed by innate lymphoid cells (ILC) and that its expression is regulated by ILC subset-specific cytokine cues in a microbiota-dependent manner. Genetic deletion or antibody blockade of CTLA-4 demonstrates that this pathway plays a key role in intestinal homeostasis and is conserved in human IBD and CPI-induced colitis (CPI-C). We propose that this population of CTLA-4-positive ILC may serve as an important target for the treatment of idiopathic and iatrogenic intestinal inflammation.

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