Phenotypic and functional changes seen in the aged adaptive immune system are primarily driven by aging of hematopoietic stem cells (HSCs), pharmacological rejuvenated aged HSCs were able to reconstituted a youthful immune system Overall design: We employed RNA-seq to assess similarities/differences between naive CD4+ T cells and CD19+ B cells isolated from RAG1-/- recipients transplanted with either young, old or old rejuvenated (CASIN treated) HSCs
Aged murine hematopoietic stem cells drive aging-associated immune remodeling.
Specimen part, Cell line, Subject
View SamplesCanonical IKK/NF-B signaling is a master regulator of inflammation and innate immunity and has been implicated in the pathogenesis of T1D. To investigate the impact of NF-B activation on -cell homeostasis and diabetes development, we generated a transgenic gain-of-function mouse model allowing conditional NF-B activation via expression of IKK2-CA (constitutively active IKK2 allele) in -cells using the tetracycline-regulated gene expression system. Pdx-1-tTA (knockin model generating Pdx-1 haploinsufficiency) driver mice were used for -cell specific transgene expression. Double transgenic IKK2-CA-pdx-1 mice develop a full-blown immune-mediated diabetes.To identify gene expression changes underlying this diabetes development pancreatic islets of diabetic IKK2-CA-Pdx-1, PDX-1 +/- and control mice were prepared and isolated total RNA was used for microarray analysis.
Long-term IKK2/NF-κB signaling in pancreatic β-cells induces immune-mediated diabetes.
Specimen part
View SamplesSplenic innate-like marginal zone B (MZB) cells are strategically positioned at the interface between the circulating blood and lymphoid tissue, where they initiate rapid immune responses to blood-borne antigens. Here, we find that selective genetic deletion of MZB cells substantially increases the follicular helper T (Tfh) cell and germinal center (GC) response to high cholesterol diet (HCD), which leads to T cell-dependent acceleration of atherosclerosis. We show that MZB cells activate a homeostatic program in response to HCD, in which upregulation of the transcription factor Atf3 plays a determinant regulatory role. Shuttling of MZB cells to the follicle is dispensable for their regulatory properties on Tfh cells. Instead, HCD promotes increased interaction between MZB and (pre-)Tfh cells outside the follicle, and upregulates MZB cell expression of Cd274 in an Atf3-dependent manner. Interaction between MZB and Tfh cells leads to Cd274-mediated suppression of Tfh cell motility, limits Tfh cell accumulation in the follicle and suppresses the pro-atherogenic Tfh/GC response. Our findings reveal a previously unsuspected role for MZB cells in the control of Tfh/GC response to a cholesterol diet, and uncover a new mechanism through which MZB cells can couple their unique metabolic and innate immune properties and use them to maintain a tolerogenic state. The results may have broad (patho)physiological implications. Overall design: Transcriptomic comparision between high-fat diet and standard chow in LDLr -/- splenic marginal zone B cells
Marginal zone B cells control the response of follicular helper T cells to a high-cholesterol diet.
No sample metadata fields
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LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.
Age, Specimen part, Treatment
View SamplesStrategy to repress autoimmunity and promote islet beta cell regeneration
LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus.
Age, Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Tissue-specific NETs alter genome organization and regulation even in a heterologous system.
Cell line, Treatment
View SamplesThe nuclear transmembrane proteins (NETs) NET29/TMEM120A, NET39/PPAPDC3 and NET47/TM7SF2 are able to reposition chromosomes towards/away from the nuclear envelope when overexpressed or knocked down in HT1080 cells. In this study we wanted to investigate the transcriptome changes after transfection of the full length NETs or a nucleoplasmic soluble fragment that does not localise to the nuclear envelope.
Tissue-specific NETs alter genome organization and regulation even in a heterologous system.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments.
Specimen part, Time
View SamplesActivation of T-cells induces dramatic changes in genome organisation and gene transcription. Here we identify changes in transcriptional profiles at 8h, 24h and 48 post activation
Constrained release of lamina-associated enhancers and genes from the nuclear envelope during T-cell activation facilitates their association in chromosome compartments.
Specimen part, Time
View SamplesGene expression in larval, early third instar eye-antenna discs was assessed to reveal an ATF4 contribution to target gene induction following COX7a knockdown. As hypothesised, these COX7a-RNAi induced target genes require the transcription factor ATF4 for induction, irrespective of concomitant Notch pathway activation through Delta over-expression.
ATF4-Induced Warburg Metabolism Drives Over-Proliferation in Drosophila.
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