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Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE123593 | GEO | 2020/10/20

REPOSITORIES: GEO

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The transcription factor C/EBPβ orchestrates dendritic cell maturation and functionality under homeostatic and malignant conditions.

Project description:Dendritic cell (DC) maturation is a prerequisite for the induction of adaptive immune responses against pathogens and cancer. Transcription factor (TF) networks control differential aspects of early DC progenitor versus late-stage DC cell fate decisions. Here, we identified the TF C/EBPβ as a key regulator for DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Upon cell-specific deletion of C/EBPβ in CD11c+MHCIIhi DCs, gene expression profiles of splenic C/EBPβ-/- DCs showed a down-regulation of E2F cell cycle target genes and associated proliferation signaling pathways, whereas maturation signatures were enriched. Total splenic DC cell numbers were modestly increased but differentiation into cDC1 and cDC2 subsets were unaltered. The splenic CD11c+MHCIIhiCD64+ DC compartment was also increased, suggesting that C/EBPβ deficiency favors the expansion of monocytic-derived DCs. Expression of C/EBPβ could be mimicked in LAP/LAP* isoform knockin DCs, whereas the short isoform LIP supported a differentiation program similar to deletion of the full-length TF. In accordance with E2F1 being a negative regulator of DC maturation, C/EBPβ-/- bone marrow-derived DCs matured much faster enabling them to activate and polarize T cells stronger. In contrast to a homeostatic condition, lymphoma-exposed DCs exhibited an up-regulation of the E2F transcriptional pathways and an impaired maturation. Pharmacological blockade of C/EBPβ/mTOR signaling in human DCs abrogated their protumorigenic function in primary B cell lymphoma cocultures. Thus, C/EBPβ plays a unique role in DC maturation and immunostimulatory functionality and emerges as a key factor of the tumor microenvironment that promotes lymphomagenesis.

| S-EPMC7584915 | biostudies-literature

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [CEBPbetaKO]

2020-10-20 | GSE123591 | GEO

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [Emu-Myc]

2020-10-20 | GSE123592 | GEO

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions

Project description:Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions

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Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [CEBPbetaKO]

Project description:Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [CEBPbetaKO]

| PRJNA509277 | ENA

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [Emu-Myc]

Project description:Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [Emu-Myc]

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Hyaluronan-based extracellular matrix under conditions of homeostatic plasticity.

Project description:Neuronal networks are balanced by mechanisms of homeostatic plasticity, which adjusts synaptic strength via molecular and morphological changes in the pre- and post-synapse. Here, we wondered whether the hyaluronic acid-based extracellular matrix (ECM) of the brain is involved in mechanisms of homeostatic plasticity. We hypothesized that the ECM, being rich in chondroitin sulfate proteoglycans such as brevican, which are suggested to stabilize synapses by their inhibitory effect on structural plasticity, must be remodelled to allow for structural and molecular changes during conditions of homeostatic plasticity. We found a high abundance of cleaved brevican fragments throughout the hippocampus and cortex and in neuronal cultures, with the strongest labelling in perineuronal nets on parvalbumin-positive interneurons. Using an antibody specific for a brevican fragment cleaved by the matrix metalloprotease ADAMTS4, we identified the enzyme as the main brevican-processing protease. Interestingly, we found ADAMTS4 largely associated with synapses. After inducing homeostatic plasticity in neuronal cell cultures by prolonged network inactivation, we found increased brevican processing at inhibitory as well as excitatory synapses, which is in line with the ADAMTS4 subcellular localization. Thus, the ECM is remodelled in conditions of homeostatic plasticity, which may liberate synapses to allow for a higher degree of structural plasticity.

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Islet Lymphocytes Maintain a Stable Regulatory Phenotype Under Homeostatic Conditions and Metabolic Stress.

Project description:T cells and B cells have been identified in human and murine islets, but the phenotype and role of islet lymphocytes is unknown. Resident immune populations set the stage for responses to inflammation in the islets during homeostasis and diabetes. Thus, we sought to identify the phenotype and effector function of islet lymphocytes to better understand their role in normal islets and in islets under metabolic stress. Lymphocytes were located in the islet parenchyma, and were comprised of a mix of naïve, activated, and memory T cell and B cell subsets, with an enrichment for regulatory B cell subsets. Use of a Nur77 reporter indicated that CD8 T cells and B cells both received local antigen stimulus, indicating that they responded to antigens present in the islets. Analysis of effector function showed that islet T cells and B cells produced the regulatory cytokine IL-10. The regulatory phenotype of islet T cells and B cells and their response to local antigenic stimuli remained stable under conditions of metabolic stress in the diet induced obesity (DIO) model. T cells present in human islets retained a similar activated and memory phenotype in non-diabetic and T2D donors. Under steady-state conditions, islet T cells and B cells have a regulatory phenotype, and thus may play a protective role in maintaining tissue homeostasis.

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Gene expression analyses of GI eosinophils under homeostatic conditions

Project description:RNA-seq was performed on eosinophils isolated from colons of naive C57/BL6 mice.

2018-10-01 | GSE106213 | GEO

Single-cell RNA-sequence of basophils under homeostatic conditions

Project description:Basophils are the least common granulocytes which represent less than 1% of peripheral blood leukocytes. Recent development of analytical tools for basophils has enabled us to understand their critical roles in allergic reactions and protection from parasitic infections. Nevertheless, the differentiation trajectory of basophils remain unclear. To explore differentiation trajectory of basophils, we conducted highly sensitive single cell RNA sequencing (scRNA-seq) of bone marrow-derived basophils (BMBAs) and basophils under homeostatic conditions. As a result, we identified previously-unappreciated pre-basophils which are located down-stream of bi-potential basophil and mast cell common precursors and upstream of mature basophils along the ontogeny of basophlis.

2023-03-21 | GSE206589 | GEO

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