Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The inositol phosphtase INPP4B sustains ILC1s and intratumoral NK cells through an AKT-driven survival pathway

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE250334 | GEO | 2024/01/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Embryonic and neonatal waves generate distinct populations of hepatic ILC1s

Project description:Group 1 innate lymphoid cells (ILCs) comprising circulating natural killer (cNK) cells and tissue-resident ILC1s are critical for host defense against pathogens and tumors. Despite a growing understanding of their role in homeostasis and disease, the ontogeny of group 1 ILCs remains largely unknown. Here, we used fate mapping and single-cell transcriptomics to comprehensively investigate the origin and turnover of group 1 ILCs. While cNK cells are continuously replaced throughout life, we uncovered tissue-dependent development and turnover of ILC1s. A first wave of ILC1s emerges during embryogenesis in the liver and transiently colonizes fetal tissues. After birth, a second wave quickly replaces ILC1s in most tissues apart from the liver, where they layer with embryonic ILC1s and persist until adulthood undergoing a unique developmental program. While embryonically-derived ILC1s give rise to a cytotoxic subset, the neonatal wave establishes a helper-like subset. Our findings uncover key ontogenic features of group 1 ILCs and their association with unique cellular identities and functions.

2022-08-19 | GSE202475 | GEO

Multi-tissue Single-Cell Analysis Deconstructs the Complexities of Mouse NK-ILC1 Programs

Project description:Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are a heterogenous group of T-bet+ innate cells that produce IFN-γ and are broadly defined as lineage–NK1.1+NKp46+ cells in mice. ILC1s definition primarily stems from studies on liver-resident and small intestinal populations. However, ILC1s in many anatomical sites, including visceral adipose tissue, salivary glands, and uterus, exhibit non-uniform programs that do not adequately overlap with those of liver or gut ILC1s or NK cells. Here, we performed single-cell RNA sequencing on murine NK1.1+NKp46+ cells from blood, spleen, lymph nodes, liver, salivary gland, uterus, visceral adipose tissue, small intestines, and several solid tumors. By including cells from an array of niches we defined tissue-specific ILC1 subsets. Moreover, we found a significant heterogeneity of circulating NK cells, due to a spectrum of proliferating, effector and migration programs, which was reduced in tumor-bearing mice, demonstrating repertoire reshaping in response to diseased conditions.

2021-05-04 | GSE158547 | GEO

scRNASeq of human innate lymphoid cells from different compartments

Project description:Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) cells and ILC1s. We identifiy a population of Ã¢Â€Âœliver-typeÃ¢Â€Â ILC1s with transcriptional, phenotypic, and functional features distinct from those of conventional and liver-resident NK cells as well as from other previously described human ILC1 subsets. LT-ILC1s were CD49a+CD94+CD200R1+, expressed the transcription factor T-BET, do not express the activating receptor NKp80, or the transcription factor EOMES. Similar to NK cells, liver-type ILC1s produce IFN-ÃŽÂ³, TNF-ÃŽÂ±, and GM-CSF; however, liver-type ILC1s also produce IL-2 and lack perforin and granzyme B. Liver- type ILC1s are expanded in cirrhotic liver tissues, and they can be produced from blood-derived ILC precursors in vitro in the presence of TGF-ÃŽÂ²1 and liver sinusoidal endothelial cells. Cells with similar signature and function can also be found in tonsil and intestinal tissues. Collectively, our study identifies and classifies a population of human cross-tissue ILC1s.

| EGAS00001006847 | EGA

Toxoplasma gondii Infection Promotes NK Cell Conversion into ILC1s and Heterogeneous ILC1 Populations

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.

2019-02-28 | GSE124577 | GEO

Identification of human cytotoxic ILC3s

Project description:Human ILCs are classically categorized into five subsets; cytotoxic CD127-CD94+ NK cells and non-cytotoxic CD127+CD94-, ILC1s, ILC2s, ILC3s and LTi cells. Here, we identify a novel subset within the CD127+ ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94+ ILCs strongly resemble conventional ILC3s in terms of phenotype, transcriptome and cytokine production, but are highly cytotoxic. IL-15 was unable to induce differentiation of CD94+ ILCs towards mature NK cells. Instead, CD94+ ILCs retained RORγt, CD127 and CD200R expression and produced IL-22 in response to IL-15. Culturing non-cytotoxic CD127+ ILC1s or ILC3s with IL-12 induced upregulation of CD94 and cytotoxic activity, effects that were not observed with IL-15 stimulation. Thus, human helper ILCs can acquire a cytotoxic program without differentiating into NK cells.

2020-09-14 | GSE147231 | GEO

Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor

Project description:Background: Innate lymphoid cells (ILCs) comprise cytotoxic NK cells and “helper” ILCs (hILCs). Human hILC development is less characterized as compared to NK cells, although all ILCs are developmentally related. It has been reported that the immunosuppressive drugs glucocorticoids (GCs) regulate ILCs function, but whether they control ILCs differentiation from hematopoietic stem cells (HSCs) is unknown. Objective: We sought to analyze the effect of GCs on ILC development from HSCs. Methods: We exploited an in vitro system to generate and expand from peripheral blood (PB) HSCs a multipotent CD56+ ILC precursor able to differentiate into NK cells, ILC1s and ILC3s. We also analyzed ex vivo, at different time points, the PB of allogeneic HSC transplantation (HSCT) recipients who were or were not treated with GCs and compared ILC subset reconstitution. Results: We show that, in vitro, GCs favor the generation of NK cells from myeloid precursors, while they strongly impair lymphoid development. In support to these data, HSCT recipients who had been treated with GCs display a lower number of circulating hILCs, including the ILCP previously identified as a systemic substrate for tissue ILC differentiation. Conclusions: GCs impair the development of the CD117+ ILCP from CD34+ HSCs, while they do not affect the further steps of ILCP differentiation towards NK cells and hILC subsets. This reflects an association of GC treatment with a marked reduction of circulating hILCs in the recipients of HSCT.

2021-11-05 | GSE186950 | GEO

Conventional NK cells and ILC1s do not influence pathogenesis of experimental glomerulonephritis

Project description:Innate lymphoid cells (ILCs) that express NK cell receptors (NCRs) and the transcription factor T-bet populate non-lymphoid tissues and are crucial in immune responses against viral infections and malignancies. Recent studies highlighted the heterogeneity of this ILC population and extended their functional spectrum to include important roles in tissue homeostasis and autoimmunity. Here, we provide detailed profiling of NCR+T-bet+ ILC populations in the murine kidney, identifying conventional NK (cNK) cells and type 1 ILCs (ILC1s) as the two major subsets. Induction of renal inflammation in a mouse model of glomerulonephritis did not substantially influence abundance or phenotype of cNK cells or ILC1s in the kidney. For functional analyses in this model, widely used depletion strategies for total NCR+ ILCs (αNK1.1 antibody application) and cNK cells (α-asGM1 serum application) were unreliable tools, since they were accompanied by significant off-target depletion of kidney NKT cells and CD8+ T cells, respectively. However, neither depletion of cNK cells and ILC1s in NKT cell-deficient mice, nor specific genetic deletion of cNK cells in Ncr1Cre/wt x Eomesfl/fl mice altered the clinical course of experimental glomerulonephritis. In summary, we show here that cNK cells and ILC1s are dispensable for initiation and progression of immune-mediated glomerular disease and advise caution in the use of standard antibody depletion methods to study NCR+ ILC function in mouse models.

2022-01-07 | GSE193001 | GEO

Systemic human ILC precursors provide a substrate for tissue ILC differentiation

Project description:Innate lymphoid cells (ILCs) represent innate versions of T helper and cytotoxic T cells that differentiate from committed ILC precursors (ILCP). Still, how ILCP relate to mature tissue-resident ILCs remains unclear. We identify ILCP that are present in the blood and all tested lymphoid and non-lymphoid human tissues. Human ILCP fail to express the signature transcription factors (TF) and cytokine outputs of mature NK cells and ILCs but are epigenetically poised to do so. Human ILCP robustly generate all ILC subsets in vitro and in vivo. While human ILCP express RAR related orphan receptor C (RORC), circulating ILCP can be found in RORC-deficient patients that retain potential for EOMES+ NK cells, T-BET+ ILC1, GATA-3+ ILC2 and for IL-22+ but not for IL-17A+ ILC3. We propose a model of tissue ILC differentiation (‘ILC-poiesis’) whereby diverse ILC subsets are generated in situ from ILCP in response to environmental stressors, inflammation and infection.

2017-03-19 | GSE90640 | GEO

Microarray data from human cultured ILC3s

Project description:Innate lymphoid cells (ILCs) are tissue-resident lymphocytes subdivided into ILC1s, ILC2s and ILC3s based on core regulatory programs and signature cytokines secreted. ILCs exhibit functional plasticity: for instance, human IL-22-producing ILC3s convert into IFN-γ-producing ILC1-like in vitro. Whether this conversion occurs in vivo is unclear. Using flow cytometry, mass cytometry and scRNAseq, here we found that ILC3s and ILC1s occupy opposite ends of a spectrum including discrete subsets in human tonsils. RNA velocity suggested strong directionality toward ILC1s for one ILC3-ILC1 intermediate cluster. Clonal analysis revealed graded ability of ILC3-ILC1 subsets to convert into ILC1-like cells. When examined in humanized mice, ILC3 acquisition of ILC1 features showed tissue-dependency. In chromatin studies, Aiolos emerged as a nuclear factor that cooperates with Tbet to repress evolutionarily conserved regulatory elements active in ILC3s. The human intestine also exhibited an ILC3–ILC1 transitional population. We conclude that conversion of ILC3s to ILC1-like occurs in vivo in human tissues, and that tissue factors and Aiolos are crucial for this process.

2019-06-18 | GSE132843 | GEO

Genome Wide Chromatin Mapping of Aiolos accessability and H3K27ac histone modifications in transfected MNK3 cells

2019-05-07 | GSE130774 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data