Gene expression in control and DOCK8 CRISPR KHYG1 NK cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE101467 | GEO | 2017/09/15
SECONDARY ACCESSION(S): PRJNA394516
REPOSITORIES: GEO
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Project description:Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here we show that mice deficient in Eri1, a conserved 3M-bM-^@M-^Y-to-5M-bM-^@M-^Y exoribonuclease that represses RNA interference, have a cell-intrinsic defect in the homeostasis and terminal maturation of NK cells. Eri1M-bM-^@M-^S/M-bM-^@M-^S NK cells show delayed acquisition of Ly49 receptors in the bone marrow and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Furthermore, antigen-specific Ly49H+ NK cells deficient in Eri1 fail to expand efficiently in mouse cytomegalovirus (MCMV) infection. Consequently, we find that Eri1 is required for immune-mediated control of MCMV titers. In contrast to NK cells, T cells deficient in Eri1 differentiate into effectors that produce high levels of Th2 cytokines. Here we identify miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. NK and T cells deficient in Eri1 display an approximately two-fold increase in all miRNAs. In Eri1-deficient T cells, ectopic expression of wildtype Eri1 is sufficient to rescue defects in both miRNA homeostasis and Th2 cytokine production. Thus mouse Eri1 negatively regulates miRNA homeostasis and is required to promote normal lymphocyte effector functions. One sample; one color design. These are six arrays from a study investigating the microRNA profile of wildtype and Eri1-deficient Th cells that is to published separately.
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2011-06-14 | E-GEOD-29930 | biostudies-arrayexpress
Project description:is involved in the formation of immune signaling complexes. To date only limited and moreover 35 conflicting data exist regarding the role of ADAP in NK cells. To extend existing knowledge we 36 investigated ADAP-dependency of NK cells in the context of in vivo infection with the intracellular 37 pathogen Listeria monocytogenes (Lm). Ex vivo analysis of infection-primed NK cells revealed 38 impaired expression of IFN-γ and chemokines as well as impaired cytotoxic capacity in NK cells 39 lacking ADAP as indicated by reduced CD107a surface expression and inefficient perforin 40 production. However, ADAP-deficiency had no global effect on NK cell morphology or intracellular 41 distribution of CD107a-containing vesicles. Proteomic definition of ADAPko and wild type NK cells 42 did not uncover obvious differences in protein composition during the steady state and moreover, 43 similar early response patterns were induced in NK cells upon infection independent of the genotype. 44 In line with protein network analyses that suggested an altered migration phenotype in naïve 45 ADAPko NK cells, in vitro migration assays uncovered significantly reduced migration of both naïve 46 as well as infection-primed ADAPko NK cells compared to wild type NK cells. We propose that this 47 migration defect might account at least in part for the fact that during in vivo infection significantly 48 lower numbers of ADAPko NK cells accumulate in the spleen i.e. the site of infection. In conclusion, 49 we show here that during systemic Lm infection in mice ADAP is essential for efficient cytokine and 50 chemokine production, cytotoxic capacity and migration of NK cells.
2020-05-27 | PXD016305 | Pride
Project description:Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here we show that mice deficient in Eri1, a conserved 3’-to-5’ exoribonuclease that represses RNA interference, have a cell-intrinsic defect in the homeostasis and terminal maturation of NK cells. Eri1–/– NK cells show delayed acquisition of Ly49 receptors in the bone marrow and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Furthermore, antigen-specific Ly49H+ NK cells deficient in Eri1 fail to expand efficiently in mouse cytomegalovirus (MCMV) infection. Consequently, we find that Eri1 is required for immune-mediated control of MCMV titers. In contrast to NK cells, T cells deficient in Eri1 differentiate into effectors that produce high levels of Th2 cytokines. Here we identify miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. NK and T cells deficient in Eri1 display an approximately two-fold increase in all miRNAs. In Eri1-deficient T cells, ectopic expression of wildtype Eri1 is sufficient to rescue defects in both miRNA homeostasis and Th2 cytokine production. Thus mouse Eri1 negatively regulates miRNA homeostasis and is required to promote normal lymphocyte effector functions.
2012-07-11 | GSE32126 | GEO
Project description:Retinoic-acid receptor-related orphan receptor-γt-positive (RORγt+) innate lymphoid cells (ILCs) produce interleukin (IL)-22 and IL-17, which are critical for protective immunity against enteric pathogens. The molecular mechanism underlying the development and survival of RORγt+ ILCs is not thoroughly understood. Here we show that Dedicator of cytokinesis 8 (DOCK8), a scaffolding protein involved in cytoskeletal rearrangement and cell migration, is essential for the protective immunity against Citrobacter rodentium. A comparative RNA sequencing-based analysis reveals an impaired induction of antimicrobial peptides in the colon of DOCK8-deficient mice, which correlates with high susceptibility to infection and a very low number of IL-22-producing RORγt+ ILCs in their GI tract. Furthermore, DOCK8-deficient RORγt+ ILCs are less responsive to IL-7 mediated signaling, more prone to apoptosis and produce less IL-22 due to a defect in IL-23-mediated STAT3 phosphorylation. Our studies reveal an unsuspected role of DOCK8 for the function, generation and survival of RORγt+ ILCs. Control and DOCK8 KO mice were infected with 2X109 CFU of Citrobacter rodentium and day 8 post infection mice were sacrificed and their colons were harvested (n=5) . Total RNA was purified from the infected colons with RNeasy mini kit (Qiagen). RNA sequencing was performed (pooled RNA sample from five mice in each group) at Genomic Core Facility Southwestern Medical Center, University of Texas.
2014-06-25 | E-GEOD-58765 | biostudies-arrayexpress
Project description:T follicular helper (Tfh) cell migration into germinal centers (GC) is essential for the generation of GC B cells and antibody responses to T dependent (TD) antigens. This process requires interactions between LFA-1 on Tfh cells and ICAMs on B cells. The mechanisms underlying defective antibody responses to TD antigens in DOCK8 deficiency are incompletely understood. We show that mice selectively lacking DOCK8 in T cells have impaired IgG antibody responses to TD antigens, decreased GC size, and reduced numbers of GC B cells. However, they develop normal numbers of Tfh cells with intact capacity for driving B cell differentiation into a GC phenotype in vitro. Notably, migration of DOCK8 deficient T cells into GCs is defective. Following TCR/CD3 ligation, DOCK8 deficient T cells have impaired LFA-1 activation and reduced binding to ICAM-1. DOCK8 is important for LFA1-dependent positioning of Tfh cells in GCs, and thereby the generation of GC B cells and IgG antibody responses to TD antigen.
2020-07-23 | GSE154897 | GEO
Project description:Background: DOCK8 deficiency is an autosomal recessive form of hyperimmunoglobulinemia E syndrome (HIES). Severe atopic dermatitis (AD) shares with DOCK8 deficiency some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. The deficiency of DOCK8 protein is potentially a life-threatening autosomal recessive HIES and only curable with bone marrow transplantation. Despite identified metabolomics and cytokine biomarkers, novel proteomics biomarkers need to be identified, as the connecting networks are critical to our understanding of this disease. Hence we performed serum proteomics profiling using LC-MSE SynaptG2. Method: Label-free untargeted proteomics analysis was used to identify potentially reliable, sensitive, and specific protein biomarkers in serum collected from DOCK8 (n=10), AD (n=9) patients, which were compared to ctrls (n=5). Results: From a total of 275 quantifiable proteins, binary comparisons between AD vs. Ctrl, DOCK8 vs. Ctrl, and DOCK8 vs. AD revealed 109, 105 and 85 dysregulated proteins, respectively. 24 among 85 proteins were specific potential biomarkers among the DOCK8 and AD groups. The sensitivity and specificity of few proteins like Claspin, Immunoglobulin kappa and heavy, complement components as potential biomarkers to distinguish between DOCK8 and AD patients were evaluated using the receiver operating characteristic curve. DOCK8 deficiency and AD groups' profiling revealed a shared role of ERK1/2 among the commonly dysregulated proteins. Conclusion: In this study, we have identified potential proteomics biomarkers and profile to distinguish between DOCK8 and AD, with possible diagnostic and therapeutic applications to help create effective interventions for managing these diseases. Further studies to confirm these associations in prospective cohorts are warranted.
2022-05-17 | PXD029052 | Pride