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ICD8a cells study

ABSTRACT: Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8a cells, characterized by expression of CD8a homodimers. iCD8a cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8a cells depends on expression of interleukin-2 receptor g chain (IL-2Rgc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8a cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8a cells in immune responses associated with the intestinal epithelium.

ORGANISM(S): Mus musculus

PROVIDER: GSE63674 | GEO | 2014/11/27

SECONDARY ACCESSION(S): PRJNA268671

REPOSITORIES: GEO

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iCD8a cells study

Project description:Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8a cells, characterized by expression of CD8a homodimers. iCD8a cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8a cells depends on expression of interleukin-2 receptor g chain (IL-2Rgc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8a cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8a cells in immune responses associated with the intestinal epithelium. Three different populations of immune cells present in the intestine epithelium of RAG-2 deficient mice were compared at the transcriptome level. These populations were defined as: a. CD45+CD8alpha+ (iCD8a cells), b. NKp46+NK1.1+ (group 1 ILC), and c.CD45+CD8alpha-CD11b+ (myeloid cells). High quality RNA was sequenced at the Vanderbilt Technologies for Advanced Genomics (VANTAGE) core using an Illumina HiSeq 2500. RAN data alignment was performed by top hat, followed by gene quantification (FPKM) using Cufflinks. Additional read count was generated using HTSeq. Differential expression analysis was carried out using both FPKM and read count-based methods. Pathway and network analyses were performed using Ingenuity.

2014-11-27 | E-GEOD-63674 | biostudies-arrayexpress

Expression data from IL-1β-stimulated immature human enterocytes treated with probiotic-conditioned media

2015-06-22 | GSE62208 | GEO

Expression data from IL-1β-stimulated immature human enterocytes treated with probiotic-conditioned media

Project description:The conditioned media from Bifidobacterium infantis (BCM) and Lactobacillus acidophilus (LCM) were reported to promote maturation of innate immune response gene expression, which explained the protective effects of probiotics in clinical necrotizing enterocolitis. We used microarray analysis to investigate the expression of genes involved in regulation of BCM and LCM in IL-1β stimulated immature human enterocytes. The H4 cells (a human nontransformed primary intestinal epithelial cell line) were pretreated with BCM or LCM (15%) for 30 minutes, and then stimulated with or without IL-1β (10 ng/mL) for 4 h. Cell media and IL-1β stimulation were negative and positive control, respectively. RNA was extracted for mcroarray analysis. A total of six treatments (triplicates for each) were included in this study. As one RNA sample in IL-1β-stimulated cells treated with BCM was dropped due to bad quality, seventeen samples were analyzed. Various treatments were compared to the nagative control (cell media alone). Genes with a fold-change ≥2 and a p value ≤ 0.05 were selected.

2015-06-22 | E-GEOD-62208 | biostudies-arrayexpress

Microfluidic Device Facilitates In Vitro Modeling of Human Neonatal Necrotizing Enterocolitis-on-a-Chip

Project description:Necrotizing enterocolitis is an intestinal disease induces rapid destruction of the epithelial monolayer of the neonatal intestine. Clinically relevant models of this disease are lacking. Using our novel microfluidic model of necrotizing enterocolitis, we characterized the response of intestinal epithelial cell-derived organoids to intestinal bacteria isolated from a neonate with fatal NEC. We subsequently used RNA-sequencing to determine the gene expression profile of these cells after 24 or 72 hours of incubation.

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Transcription profiling time series of the effects of hypoxia, breast and formula feeding on a Rattus norvegicus model of necrotizing enterocolitis

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2007-10-11 | E-GEOD-491 | biostudies-arrayexpress

Impact of RUNX3 KO on H3K27ac abundance in human NK cells

Project description:The surface receptor CD8a is present on 20-80% of human (but not mouse) NK cells, yet its function on NK cells remains poorly understood. CD8a expression on donor NK cells was associated with a lack of therapeutic responses for leukemia patients in prior studies, thus we hypothesized that CD8a may impact critical NK cell functions. Here, we discovered that CD8a- NK cells had improved control of leukemia in xenograft models, compared to CD8a+ NK cells, likely due to an enhanced capacity for proliferation. Unexpectedly, CD8a expression was induced on approximately 30% of previously CD8a- NK cells following IL-15 stimulation. These ‘induced’ CD8a+ (‘iCD8a+’) NK cells had the greatest proliferation, responses to IL-15 signaling, and metabolic activity, compared to those that sustained existing CD8a expression (‘sustained CD8a+) or those that remained CD8a- (‘persistent CD8a-‘). These iCD8a+ cells originated from an IL-15Rb high NK cell population, with CD8a expression dependent on the transcription factor RUNX3. Moreover, CD8A CRISPR/Cas9 deletion resulted in enhanced responses through the activating receptor NKp30, possibly by modulating KIR inhibitory function. Thus, CD8a status identifies human NK cell capacity for IL-15-induced proliferation and metabolism in a time-dependent fashion and exhibits a suppressive effect on NK cell activating receptors

2024-06-20 | GSE263686 | GEO

Neonatal necrotizing enterocolitis-associated DNA methylation signatures in the colon are evident in stool samples of affected individuals

Project description:Neonatal necrotizing enterocolitis (NEC) is a deadly and unpredictable gastrointestinal disease, for which no biomarkers exist. We aimed to describe the methylation patterns in stool and colon from infants with NEC.

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The transcription factor GATA3 is critical for the development of all IL-7Ra-expressing innate lymphoid cells (ILCs) and maintenance of type 2 ILCs

Project description:Innate lymphoid cells (ILCs) play critical roles during innate immune responses to pathogens and lymphoid organ development. IL-7Ra+ ILC subsets, similar to T helper (Th) cell subsets, produce distinctive effector cytokines. The molecular control of IL-7Ra+ ILC development and maintenance has yet to be dissected. Here we report that GATA3 is indispensable for the development of all IL-7Ra+ ILC subsets and T cells. Gata3 conditional deficient mice have no lymph nodes and are susceptible to Citrobactor rodentium infection. Genome-wide gene analyses indicate that GATA3 regulates similar set of cytokines and receptors in ILC2s and Th2 cells and is critical for the maintenance of ILC2s. Thus, GATA3 plays parallel roles in establishing and regulating both adaptive and innate lymphocytes. To identify GATA3 regulated genes in type 2 innate lymphoid cells by tamoxifen-mediated acute deletion of Gata3 gene.

2014-03-13 | E-GEOD-47851 | biostudies-arrayexpress