Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Conventional NK cells and ILC1 are partially ablated in the livers of Ncr1 iCreTbx21 fl/fl mice.

ABSTRACT: Mouse liver contains both Eomes-dependent conventional natural killer (cNK) cells and Tbet-dependent liver-resident type I innate lymphoid cells (ILC1). In order to better understand the role of ILC1, we attempted to generate mice that would lack liver ILC1, while retaining cNK, by conditional deletion of Tbet in NKp46+ cells. Here we report that the Ncr1 iCreTbx21 fl/fl mouse has a roughly equivalent reduction in both the cNK and ILC1 compartments of the liver, limiting its utility for investigating the relative contributions of these two cell types in disease models. We also describe the phenotype of these mice with respect to NK cells, ILC1 and NKp46 + ILC3 in the spleen and small intestine lamina propria.

SUBMITTER: Cuff AO

PROVIDER: S-EPMC5543419 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Conventional NK cells and ILC1 are partially ablated in the livers of Ncr1 iCreTbx21 fl/fl mice.

Cuff Antonia O AO Male Victoria V

Wellcome open research 20170705

Mouse liver contains both Eomes-dependent conventional natural killer (cNK) cells and Tbet-dependent liver-resident type I innate lymphoid cells (ILC1). In order to better understand the role of ILC1, we attempted to generate mice that would lack liver ILC1, while retaining cNK, by conditional deletion of Tbet in NKp46+ cells. Here we report that the Ncr1 iCreTbx21 fl/fl mouse has a roughly equivalent reduction in both the cNK and ILC1 compartments of the liver, limiting it ...[more]

PMID: 28815219

Similar Datasets

Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells.

Project description:Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here, we describe Toxoplasma gondii infection converts NK cells into ILC1-like cells that are distinct from both steady-state NK cells and ILC1s in uninfected mice. These cells were Eomes-dependent, indicating that NK cells can give rise to Eomes- Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

| S-EPMC6703900 | biostudies-literature

NK/ILC1 cells mediate neuroinflammation and brain pathology following congenital CMV infection.

Project description:Congenital human cytomegalovirus (cHCMV) infection of the brain is associated with a wide range of neurocognitive sequelae. Using infection of newborn mice with mouse cytomegalovirus (MCMV) as a reliable model that recapitulates many aspects of cHCMV infection, including disseminated infection, CNS infection, altered neurodevelopment, and sensorineural hearing loss, we have previously shown that mitigation of inflammation prevented alterations in cerebellar development, suggesting that host inflammatory factors are key drivers of neurodevelopmental defects. Here, we show that MCMV infection causes a dramatic increase in the expression of the microglia-derived chemokines CXCL9/CXCL10, which recruit NK and ILC1 cells into the brain in a CXCR3-dependent manner. Surprisingly, brain-infiltrating innate immune cells not only were unable to control virus infection in the brain but also orchestrated pathological inflammatory responses, which lead to delays in cerebellar morphogenesis. Our results identify NK and ILC1 cells as the major mediators of immunopathology in response to virus infection in the developing CNS, which can be prevented by anti-IFN-γ antibodies.

| S-EPMC7918636 | biostudies-literature

RNA-seq of splenic natural killer cells from Hif1a(fl/fl) and Ncr1(Cre)Hif1a(fl/fl) mice

Project description:Alteration of gene expression in natural killer cells triggers by HIF-1a loss.

2022-08-22 | E-MTAB-12082 | biostudies-arrayexpress

RNA-seq of colonic tissues from Hif1a(fl/fl) and Ncr1(Cre)Hif1a(fl/fl) mice

Project description:Global alterations in gene expression in the colon triggered by HIF-1a loss in NKp46+ cells.

2021-12-10 | E-MTAB-11214 | biostudies-arrayexpress

JAK Inhibition Differentially Affects NK Cell and ILC1 Homeostasis.

Project description:Janus kinase (JAK) inhibitors are widely used in the treatment of multiple autoimmune and inflammatory diseases. Immunologic and transcriptomic profiling have revealed major alterations on natural killer (NK) cell homeostasis associated with JAK inhibitions, while information on other innate lymphoid cells (ILCs) is still lacking. Herein, we observed that, in mice, the homeostatic pool of liver ILC1 was less affected by JAK inhibitors compared to the pool of NK cells present in the liver, spleen and bone marrow. JAK inhibition had overlapping effects on the transcriptome of both subsets, mainly affecting genes regulating cell cycle and apoptosis. However, the differential impact of JAK inhibition was linked to the high levels of the antiapoptotic gene Bcl2 expressed by ILC1. Our findings provide mechanistic explanations for the effects of JAK inhibitors on NK cells and ILC1 which could be of major clinically relevance.

| S-EPMC6930870 | biostudies-literature

Comparison of NK cells and ILC1 in lean versus obese mouse livers by RNASeq

Project description:Mice were weaned onto standard RM1 diet or onto a highly palatable obesogenic diet (824018 – ‘45% AFE fat) supplemented with condensed milk. After 12 weeks, mice were killed, and liver NK cells (Lin- NK1.1+ CD49a- CD49b+) or ILC1 (Lin- NK1.1+ CD49a+ CD49b-) were sorted. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed.

2019-03-13 | GSE122828 | GEO

RNA-seq of small intestine tissues from Hif1a(fl/fl) and Ncr1(Cre)Hif1a(fl/fl) mice

Project description:Global alterations in gene expression in the small intestine triggered by HIF-1a loss in NKp46+ cells.

2021-12-10 | E-MTAB-11213 | biostudies-arrayexpress

RNA-seq of small intestine tissues from VHL(fl/fl) and Ncr1(Cre)VHL(fl/fl) mice

Project description:Global alterations in gene expression in the small intestine triggered by HIF-1a activation in NKp46+ cells.

2021-12-10 | E-MTAB-11212 | biostudies-arrayexpress

SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-? signaling.

Project description:Among the features that distinguish type 1 innate lymphoid cells (ILC1s) from natural killer (NK) cells is a gene signature indicative of 'imprinting' by cytokines of the TGF-? family. We studied mice in which ILC1s and NK cells lacked SMAD4, a signal transducer that facilitates the canonical signaling pathway common to all cytokines of the TGF-? family. While SMAD4 deficiency did not affect ILC1 differentiation, NK cells unexpectedly acquired an ILC1-like gene signature and were unable to control tumor metastasis or viral infection. Mechanistically, SMAD4 restrained non-canonical TGF-? signaling mediated by the cytokine receptor TGF?R1 in NK cells. NK cells from a SMAD4-deficient person affected by polyposis were also hyper-responsive to TGF-?. These results identify SMAD4 as a previously unknown regulator that restricts non-canonical TGF-? signaling in NK cells.

| S-EPMC5712491 | biostudies-literature

Umbilical cord blood-derived ILC1-like cells constitute a novel precursor for mature KIR+NKG2A- NK cells.

Project description:Despite their identification several years ago, molecular identity and developmental relation between human ILC1 and NK cells, comprising group 1 ILCs, is still elusive. To unravel their connection, thorough transcriptional, epigenetic, and functional characterization was performed from umbilical cord blood (CB). Unexpectedly, ILC1-like cells lacked Tbet expression and failed to produce IFN?. Moreover, in contrast to previously described ILC1 subsets they could be efficiently differentiated into NK cells. These were characterized by highly diversified KIR repertoires including late stage NKG2A-KIR+ effector cells that are commonly not generated from previously known NK cell progenitor sources. This property was dependent on stroma cell-derived Notch ligands. The frequency of the novel ILC1-like NK cell progenitor (NKP) significantly declined in CB from early to late gestational age. The study supports a model in which circulating fetal ILC1-like NKPs travel to secondary lymphoid tissues to initiate the formation of diversified NK cell repertoires after birth.

| S-EPMC7358013 | biostudies-literature