The inositol phosphtase INPP4B sustains ILC1s and intratumoral NK cells through an AKT-driven survival pathway
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1053379 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27227301_1.fastq.gz | Fastqsanger.gz | |||
| SRR27227301_2.fastq.gz | Fastqsanger.gz | |||
| SRR27227302_1.fastq.gz | Fastqsanger.gz | |||
| SRR27227302_2.fastq.gz | Fastqsanger.gz | |||
| SRR27227303_1.fastq.gz | Fastqsanger.gz |
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Project description:Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using a scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not circulating NK cells at steady-state. Inpp4b-deficient cells display increased rates of apoptosis and reduced activation of the pro-survival molecule AKT. Furthermore, expression of Inpp4b by NK/ILC1s is necessary for their presence in the intratumoral environment and lack of Inpp4b impairs antitumor immunity. These findings highlight INPP4B as a novel regulator of tissue residency and antitumor function in ILC1s and NK cells.
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Project description:Innate lymphoid cells (ILCs) are a heterogeneous population of lymphocytes that coordinate early immune responses and maintain tissue homeostasis. Type 1 innate immune responses are mediated by natural killer (NK) cells and group 1 ILCs (ILC1s). Despite their shared features, NK cells and ILC1s display profound differences among various tissue microenvironments. Here, we identify the inositol polyphosphatase INPP4B as a hallmark feature of tissue-resident ILC1s and intratumoral NK cells using an scRNA-seq atlas of tissue-associated and circulating NK/ILC1s. Conditional deletion of Inpp4b in ILC1s and NK cells reveals that it is necessary for the homeostasis of tissue-resident ILC1s but not circulating NK cells at steady-state. Inpp4b-deficient cells display increased rates of apoptosis and reduced activation of the prosurvival molecule AKT. Furthermore, expression of Inpp4b by NK/ILC1s is necessary for their presence in the intratumoral environment, and lack of Inpp4b impairs antitumor immunity. These findings highlight INPP4B as a novel regulator of tissue residency and antitumor function in ILC1s and NK cells.
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Project description:RNA sequencing demonstrated that liver Ly49E+ and Ly49E- ILC1s exhibited unique transcriptional profiles and phenotypic features. scRNA-seq analysis revealed heterogeneity within both cNK and ILC1 subsets in liver. cNK cells could be further divided into three clusters, which corresponded to different developmental stages. Ly49E expression could dissect ILC1s into two subsets: Ly49E+ ILC1s and Ly49E- ILC1s, which exhibited different functional characteristics.
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Project description:Innate lymphoid cells (ILCs) comprise several subsets that were originally classified based on their cytokine production profiles. Natural killer (NK) cells and type 1 ILCs (ILC1s) were initially classified together, but recent data supported their separation into different lineages. Here we describe how infection with the parasite Toxoplasma gondii induces changes to NK1.1+ NKp46+ cells that persist independent of ongoing infection. Notably, there is an expansion of Eomes– CD49a+ cells that superficially resemble ILC1s, but express unique genes, circulate throughout the vasculature, and possess distinct epigenetic marks. Single-cell RNA sequencing confirms T. gondii-induced Eomes– CD49a+ cells are distinct from both conventional NK cells and ILC1s. Furthermore, there is heterogeneity within this population, as both conventional NK cells and ILC1s contribute to their formation. Indeed, downregulation of Eomes within conventional NK cells accounts for most T. gondii-induced Eomes– CD49a+ cells, indicating that NK cells can give rise to cells resembling ILC1s during infection.
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Project description:Heterogeneity of liver group 1 ILC1s
| PRJNA721197 | ENA