Gut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance. Overall design: Transcriptomic analysis of fibroblastic stromal cells of skin-draining and intestinal-draining lymph nodes from endogenous and transplanted lymph nodes at the popliteal fossa.
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
Cell line, Subject
View SamplesGut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance. Overall design: Transcriptomic analysis of resident dendritic cells of skin-draining and intestinal-draining lymph nodes from endogenous and lymph nodes transplanted to the popliteal fossa.
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
Cell line, Subject
View SamplesGut-draining mesenteric lymph nodes (mLNs) play a key role in peripheral tolerance towards food and commensal antigens by providing an optimal microenvironment for efficient de novo induction of Foxp3+ regulatory T cells (Tregs). We recently identified mLN stromal cells as critical cellular players in this process and demonstrated that their tolerogenic properties are imprinted by microbiota. Here, we show that this imprinting process already takes place in the neonatal phase and renders the mLN stromal cell compartment resistant to inflammatory perturbations later in life. Utilizing LN transplantation, RNA-seq and single-cell RNA-seq allowed identification of stably imprinted expression signatures in mLN fibroblastic stromal cells. We dissected common stromal cell subsets across gut-draining mLNs and skin-draining LNs with location-specific immunomodulatory functions, such as subset-specific expression of Aldh1a2/3. Accordingly, mLN stromal cells shaped resident dendritic cells to attain high Treg-inducing capacity in a Bmp2-dependent manner. Thus, crosstalk between mLN stromal and resident dendritic cells provides a robust feedback mechanism for the maintenance of intestinal tolerance. Overall design: Transcriptomic analysis of migratory dendritic cells of skin-draining and intestinal-draining lymph nodes from endogenous and lymph nodes transplanted to the popliteal fossa.
Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
Specimen part, Subject
View SamplesRight ventricular failure (RVF) due to pressure load is a major cause of death in congenital heart diseases and pulmonary hypertension. The mechanisms of RVF are yet unknown. Research is hampered by the lack of a good RVF model. Our aim was to study the pathophysiology of RVF in a rat model of chronic pressure load.
Clinical symptoms of right ventricular failure in experimental chronic pressure load are associated with progressive diastolic dysfunction.
Sex, Specimen part
View SamplesAffymetrix Human Genome U133A platform was used to obtain gene expression profiles of 28 pathologically and clinically well characterized adenocarcinomas of the lung. In addition, EGFR status was determined by fluorescent in situ hybridization and immunohistochemistry.
Gene expression profiles of lung adenocarcinoma linked to histopathological grading and survival but not to EGF-R status: a microarray study.
Specimen part
View SamplesThe plasma protein FHR1 induces release of inflammatory cytokines IL-1ß, IL-6, IL-18 or TNFa from blood-derived human monocytes. RNA sequencing was performed from RNA of BSA- or FHR1-treated monocytes from 4 different donors. In response to FHR1, 522 monocytic genes were upregulated (gene ontology enrichment analysis), including 35 inflammation related genes, e.g. TNF. Also, G protein-coupled receptors such as EMR2/ADGRE2 were upregulated in response to FHR1. Overall design: Blood-derived monocytes were treated with BSA or FHR1, after 4h RNA was isolated. RNA of 4 donors were combined and sequenced.
Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies.
Specimen part, Treatment, Subject
View SamplesIn most embryos, the mid-blastula transition is a complex process featuring maternal RNA degradation, cell cycle pause, zygotic transcriptional activation and morphological changes. The nucleocytoplasmic (N/C) ratio has been proposed to control the multiple events at MBT. To understand the global transcriptional response to the changes of the N/C ratio, we profiled wild type and haploid embryos using cDNA microarrays at three developmental stages.
Coupling of zygotic transcription to mitotic control at the Drosophila mid-blastula transition.
No sample metadata fields
View SamplesKaposis sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response.
Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor 3 inhibits gamma interferon and major histocompatibility complex class II expression.
Specimen part, Cell line
View SamplesAssessment of chemo- and radiation therapy-naïve biopsy-confirmed invasive human breast tumors by RNAseq. Overall design: 103 total samples from 63 unique patients. Clinical details were provided only for the 50 samples in current publication. However, all 103 samples were analyzed together.
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.
Age, Specimen part, Disease stage, Subject
View SamplesThe homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. Since these circulating atypical B cells in the blood of CVID patients could not be assigned to any certain B cell differentiation stage in the periphery, they were designated as CD21low B cells. Although, CD21low B cells are polyclonal and unmutated IgM+IgD+ B cells like naive B cells in the peripheral blood, they reveal several distinct phenotypic and functional features.
Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells.
Specimen part, Disease
View Samples