The transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1 and STAT1, differ with regard to a C-terminal transactivation domain, which is absent in STAT1. Dimers of STAT1 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1. Contrasting this view, generation and analysis of mice deficient for either STAT1 or STAT1 demonstrated transcriptional activity of the STAT1 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1 and STAT1 in response to IFN. Consistently, both isoforms mediated protective, IFN-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1 and STAT1 were largely redundant for transcriptional responses to IFN/ and for IFN/-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity.
STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity.
Specimen part
View SamplesThe type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 play critical roles in stimulating innate and adaptive immune responses required for resistance to helminth infection and promotion of allergic inflammation, metabolic homeostasis and tissue repair. Group 2 innate lymphoid cells (ILC2s) are a potent source of type 2 cytokines and while significant advances have been made in understanding the cytokine milieu that promotes ILC2 responses, there are fundamental gaps in knowledge regarding how ILC2 responses are regulated by other stimuli. In this report, we demonstrate that ILC2s in the gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU). In contrast to other hematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation and secretion of type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gaq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1-/- mice compared to control mice. Further, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU-NMUR1 neuronal signaling circuit provides a selective and previously unrecognized mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites. Overall design: To assess changes in gene expression in ILC2s due to NMU treatment, RNAseq was performed on 3 samples from NMU-treated mice and 4 samples from PBS-treated mice.
The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation.
Specimen part, Cell line, Treatment, Subject
View SamplesThe type 2 cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13 play critical roles in stimulating innate and adaptive immune responses required for resistance to helminth infection and promotion of allergic inflammation, metabolic homeostasis and tissue repair. Group 2 innate lymphoid cells (ILC2s) are a potent source of type 2 cytokines and while significant advances have been made in understanding the cytokine milieu that promotes ILC2 responses, there are fundamental gaps in knowledge regarding how ILC2 responses are regulated by other stimuli. In this report, we demonstrate that ILC2s in the gastrointestinal tract co-localize with cholinergic neurons that express the neuropeptide neuromedin U (NMU). In contrast to other hematopoietic cells, ILC2s selectively express the NMU receptor 1 (NMUR1). In vitro stimulation of ILC2s with NMU induced rapid cell activation, proliferation and secretion of type 2 cytokines IL-5, IL-9 and IL-13 that was dependent on cell-intrinsic expression of NMUR1 and Gaq protein. In vivo administration of NMU triggered potent type 2 cytokine responses characterized by ILC2 activation, proliferation and eosinophil recruitment that was associated with accelerated expulsion of the gastrointestinal nematode Nippostrongylus brasiliensis or induction of lung inflammation. Conversely, worm burden was higher in Nmur1-/- mice compared to control mice. Further, use of gene-deficient mice and adoptive cell transfer experiments revealed that ILC2s were necessary and sufficient to mount NMU-elicited type 2 cytokine responses. Together, these data indicate that the NMU-NMUR1 neuronal signaling circuit provides a selective and previously unrecognized mechanism through which the enteric nervous system and innate immune system integrate to promote rapid type 2 cytokine responses that can induce anti-microbial, inflammatory and tissue-protective type 2 responses at mucosal sites. Overall design: Transcriptional differences between ILC2s and ILC3s were determined by RNAseq using 3 ILC2 samples and 3 ILC3 samples.
The neuropeptide neuromedin U stimulates innate lymphoid cells and type 2 inflammation.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression in response to Influenza A (PR8) infection
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View SamplesWe measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA.
Common genetic mechanisms of blood pressure elevation in two independent rodent models of human essential hypertension.
No sample metadata fields
View SamplesWe performed Affymetrix MG-U74Av2 GeneChip experiements on mRNA from the adrenal glands of the BPH hypertensive and BPL hypotensive mouse strains. All mice were aged-matched at 5 weeks. We obtained the mice from Jackson Laboratories, Bar Harbor, ME.
Neuroendocrine transcriptome in genetic hypertension: multiple changes in diverse adrenal physiological systems.
No sample metadata fields
View SamplesNote: GSE4063 and GSE4065 are not directly comparable.
Opposite transcriptional regulation in skeletal muscle of AMP-activated protein kinase gamma3 R225Q transgenic versus knock-out mice.
Sex, Specimen part
View Samples