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Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Bulk RNA-seq]

ABSTRACT: Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Bulk RNA-seq]

PROVIDER: PRJNA996578 | ENA |

REPOSITORIES: ENA

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Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease

Project description:Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease

| PRJNA996582 | ENA

Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Spatial Transcriptomics]

Project description:Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Spatial Transcriptomics]

| PRJNA996584 | ENA

Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Bulk RNA-seq]

Project description:Inflammatory skin diseases are spurred by unchecked immune-epithelial circuits. Although the function of cytokine and chemokine signals in facilitating this crosstalk is well established, the specific metabolic mediators involved and their simultaneous contribution to dysregulation of these two distinct cellular compartments is unclear. Here, we employed scRNA-seq, spatial transcriptomics, and immunofluorescence across multiple disease indications to elucidate a dysfunctional epithelial state marked by Hypoxia Inducible Factor 1 alpha (HIF1⍺). Ex vivo HIF1⍺ blockade of human Psoriasis (PsO) lesions led to a reduction in pathological gene expression via modulation of glucose metabolism. Epidermal-specific loss of HIF1⍺ or its transcriptional target, glucose transporter 1, curtailed both epidermal pathology and the cutaneous immune response in murine PsO. Glycolytic metabolism sustained epithelial hyperproliferation and differentiation, while lactate, its terminal product, was crucial for sustaining Type 17 response. Notably, inhibition of lactate dehydrogenase A or the lactate transporters MCT1/4 selectively attenuated the Type 17 response, underscoring a divergent requirement for glucose and lactate in epithelial and immune cells, respectively. Collectively, these findings identify therapeutically targetable immune-epithelial circuits by unveiling a remarkable coordination of metabolic processed between the epithelial and immune compartments in inflammatory skin disease.

2024-04-01 | GSE237767 | GEO

Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Spatial Transcriptomics]

Project description:Inflammatory skin diseases are spurred by unchecked immune-epithelial circuits. However, the specific metabolic factors involved in crosstalk and their impact on the dysregulation of these two cellular components are not well understood. To better decipher the metabolic factors involved in psoriasis, we employed spatial transcriptomics (ST), a ground-breaking technology that precisely maps gene expression from histologically-intact tissue sections. These findings identify therapeutically targetable metabolic vulnerabilities in inflammatory skin disease by unveiling a remarkable coordination of metabolic processes between the epithelial and immune compartments.

2024-04-01 | GSE237771 | GEO

Dickkopf1 fuels inflammatory cytokine responses

Project description:Dickkopf1 fuels inflammatory cytokine responses

| PRJNA897934 | ENA

Dickkopf1 fuels inflammatory cytokine responses

Project description:Many human diseases, including cancer, share an inflammatory component but the molecular underpinnings remain incompletely understood. We report that physiological and pathological Dickkopf1 (DKK1) activity fuels inflammatory cytokine responses in cell models, mice and humans. DKK1 maintains the elevated inflammatory tone of cancer cells and is required for mounting cytokine responses following ligation of toll-like and cytokine receptors. DKK1-controlled inflammation derives from cell-autonomous mechanisms, which involve SOCS3-restricted, nuclear RelA (p65) activity. We translate these findings to humans by showing that genetic DKK1 variants are linked to elevated cytokine production across healthy populations. Finally, we find that genetic deletion of DKK1 but not pharmacological neutralization of soluble DKK1 ameliorates inflammation and disease trajectories in a mouse model of endotoxemia. Collectively, our study identifies a cell-autonomous function of DKK1 in the control of the inflammatory response, which is conserved between malignant and non-malignant cells and may be exploited therapeutically in the future.

2022-11-10 | GSE217231 | GEO

Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-04-01 | GSE237772 | GEO

Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids

Project description:Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids

| PRJNA1053278 | ENA

Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids

Project description:Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids

| PRJNA1053280 | ENA

Efferocytosis fuels malignant pleural effusion through TIMP1

Project description:Malignant Pleural Effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. The median survival is 3-12 months and no effective treatments are currently available. Immune-based therapies have failed until now, reflecting our insufficient understanding of the basic immunological mechanisms leading to MPE progression. Here, we show that phagocytosis of apoptotic cells in the pleural cavity fuels the progression of MPE. We found that efferocytosis through the receptor tyrosine kinases AXL and MERTK in macrophages led to the production of IL-10. Using single cell RNA-Seq, we revealed that IL-10 is indeed produced by four distinct pleural cavity macrophage subpopulations characterized by different metabolic states and cell chemotaxis properties. In turn, IL-10 acts on dendritic cells (DCs) inducing the production of tissue inhibitor of metalloproteinases 1 (TIMP1). Genetic ablation of AXL and MERTK in macrophages or IL-10 receptor in DCs or TIMP1 significantly reduced MPE progression. Taken together, our results delineate an inflammatory cascade – from the clearance of apoptotic cells by macrophages, to production of IL-10, to induction of TIMP1 in DCs – that facilitates MPE progression. This inflammatory cascade offers a series of targets for therapies which aim at preventing or treating MPE.

2021-08-24 | GSE172455 | GEO

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