Tissue-Resident Natural Killer (NK) Cells Are Cell Lineages Distinct From Thymic and Conventional Splenic NK Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Maxim Artyomov
PROVIDER: E-GEOD-52047 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. Liver NK 1.1+CD49+, liver NK 1.1+CD49-, spleen NK 1.1+ CD49- populations of NK cells were sorted with FACS pooling cells from individual mice to end up with ~100k cells for each samples. mRNA was derived from lysates using Invitrogen oligo-dT beads
2014-04-26 | E-GEOD-52043 | biostudies-arrayexpress
Project description:Natural killer (NK) cells belong to the innate immune system where they can control virus infections and developing tumors by cytotoxicity and production of inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells found in the spleen. Recently, we described two populations of NK cells within the liver, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, the lineage relationship of trNK to cNK cells was unclear because trNK cells display a phenotype associated with immature, developing cNK cells. Moreover, liver trNK cells could be related to thymic NK cells or alternatively, a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis of mice deficient in several transcription factors to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells, especially because they do not require NFIL3 (E4BP4), the previously described NK cellspecification factor. Analysis of other tissues indicate the presence of trNK cells in skin and uterus with different transcription factor requirements. Thus, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. Liver DX5-CD49+, liver DX5+CD49-, spleen DX5+ CD49- populations of NK cells were sorted with FACS pooling cells from individual mice to end up with ~100k cells for each samples. mRNA was derived from lysates using Invitrogen oligo-dT beads
2014-04-26 | E-GEOD-52045 | biostudies-arrayexpress
Project description:Macrophages polarize to divergent functional phenotypes depending on their microenvironment in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified 7 major (novel and known) regulatory modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included: inflammatory variant of the aspartate-arginosuccinate shunt; TCA cycle break at Idh expression accompanied by citrate accumulation and production of itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine in polarization, providing nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation results in significant M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization. Bone-marrow derived macrophages were generated from C57BL/6 mice were plated at ~100k cells per well in 96-well plate and stimulated with either Il4 or combination of LPS&IFNg or left unstimulated for 24 h mRNA was derived from lysates using Invitrogen oligo-dT beads
2014-05-30 | E-GEOD-53053 | biostudies-arrayexpress
Project description:The NK cell pool is composed of distinct NK cell subsets with divergent phenotypic and functional features. In order to determine whether DX5- and DX5+ NK cells from murine livers represent different NK cell subsets, DX5- and DX5+ liver NK cells of adult mice were respectively sorted for gene expression analysis using the Affymetrix GeneChip Mouse Genome 430 2.0 arrays. DX5-NK1.1+CD3- cells and DX5+NK1.1+CD3- cells were sorted from the liver of naive B6 wild-type mice. RNA of each sample was then extracted and hybridized on Affymetrix microarrays to detail differences between DX5- and DX5+ liver NK cells in gene expression.
2013-01-09 | E-GEOD-43339 | biostudies-arrayexpress
Project description:Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation mechanism accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the downstream pro-inflammatory IL-1β-HIF1a axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions via its effect on succinate dehydrogenase, by inhibiting conversion of succinate to fumarate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1-/- mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, changes in mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages. Experiment 1: mature WT BMDM were treated for 12h with 0.25 mM dimethyl itaconate (DI) or vehicle (Unst) and then stimulated with LPS (E. coli 0111:B4; 100 ng/ml, 4h) (DI+LPS; LPS); Experiment 2: mature Irg1-/- BMDM were stimulated with LPS (E. coli 0111:B4; 100 ng/ml) and murine recombinant IFNg (50 ng/ml) for 24h.
2016-07-01 | E-GEOD-82043 | biostudies-arrayexpress
Project description:Type 1 interferons (IFNs) induce complex responses that can be beneficial or deleterious, depending on context. Greater understanding of the mechanisms of action of these cytokines could allow new therapeutic approaches. We found that type 1 IFNs induced changes in cellular metabolism that were critical for changes in target cell function. This was apparent in plasmacytoid dendritic cells, which are specialized for type 1 IFN production, where toll-like receptor-9 (TLR9)-dependent activation was found to be dependent on increased fatty acid oxidation (FAO) and oxidative phosphorylation (OXPHOS) induced by autocrine signaling through the type 1 IFN receptor (IFNAR). Type 1 IFNs also induced FAO/OXPHOS in non-hematopoietic cells and were found to be responsible for increased FAO/OXPHOS in virus-infected cells. Increased FAO/OXPHOS in response to IFNAR signaling was regulated by the nuclear receptor PPARα. Our findings reveal PPARα/FAO/OXPHOS as potential targets to therapeutically modulate downstream effects of type 1 IFNs. mRNA profiles of overnight stimulated plasmacytoid dendritic cells, activated with CpG or INFa. Samples analyzed in triplicate, with HiSeq 2500 byâ/ 50bpX25bp pair-end sequencing
2016-07-01 | E-GEOD-81889 | biostudies-arrayexpress
Project description:Gene-expression microarray datasets generated as part of the Immunological Genome Project (ImmGen). Primary cells from multiple immune lineages are isolated ex-vivo, primarily from young adult B6 male mice, and double-sorted to >99% purity. RNA is extracted from cells in a centralized manner, amplified and hybridized to Affymetrix 1.0 ST MuGene arrays. Protocols are rigorously standardized for all sorting and RNA preparation. Data is released monthly in batches of cell populations. This Series record provides access to Immunological Genome Project data submitted to GEO.
2009-05-02 | E-GEOD-15907 | biostudies-arrayexpress
Project description:We analyzed gene expression profiles of IL-18 generated murine NK cells in comparison to unstimulated, freshly isolated splenic NK cells. We identified a set of 1414 Affymetrix probe sets showing significant misregulation (Welch's T-test, p<0.05; Benjamini-Hochberg FDR corrected). IL-18 generated as well as unstimulated NK cells were isolated in three independent preparations and used for RNA extraction and hybridization on Affymetrix microarrays.
2012-07-10 | E-GEOD-33627 | biostudies-arrayexpress
Project description:We identified differences in the distribution of three group 1 ILC subsets in the mouse uterus. The dynamic distribution of g1 ILC subsets in the uterus at key stages of reproductive life may reflect subset-specific functions and emphasised the need for detailed characterisation of each subset
2018-10-05 | E-MTAB-6812 | biostudies-arrayexpress
Project description:The microarray was designed in order to detect transcriptional similarities/differences between innate immune cells (ILCs) in the lamina propria (N;L;R) and a putative precursor cell type detected in the bone marrow (P) of untreated mice in steady-state.
2012-10-18 | E-MEXP-3743 | biostudies-arrayexpress