Chromatin accessibility of different Kupffer cell subsets in a mycobacterial infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE279608 | GEO | 2026/04/09
REPOSITORIES: GEO
Similar Datasets
Project description:Kupffer cells can be distinguished in three subpopulations during mycobacterial infection based on the expression of Tim4 and the fluorochrome tdTomato within Clec4fCre-tdTomato-NLS: ROSA26EYFP mice. These subpopulations differ in their origin and tissue localization. The aim of this scRNA sequencing was to understand the heterogeneity of macrophages and monocytes during the peak of the infection (4 weeks) and the resolution (10 weeks) and understand their dynamics.
2026-06-04 | GSE282492 | GEO
Project description:Kupffer cells can be distinguished in three subpopulations during mycobacterial infection, based on the expression of Tim4 and the fluorochrome tdTomato within Clec4fCre-tdTomato-NLS: ROSA26EYFP mice. These subpopulations differ in their origin and tissue localization. The aim of this bulk RNA sequencing was to profile the subsets and identify marker genes, as well as to interfer functional differences.
2026-04-09 | GSE273160 | GEO
Project description:Kupffer cells (KCs) are the largest tissue resident macrophage population in direct contact with blood and thus with circulating lipoproteins. How KCs homeostasis is affected by the build-up of cholesterol-rich lipoproteins in the context of hypercholesterolemia has been poorly investigated. In this study, 5-month-old LDL receptor deficient (C57BL6J background) male mice were subjected to chow diet or a cholesterol-rich (HC) diet for four days to induce hypercholesterolemia. RNA sequencing was then performed on cell sorted KCs.
2024-09-05 | E-MTAB-12611 | biostudies-arrayexpress
Project description:Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages long known for their scavenger and phagocytic functions. KCs are also able to present antigen to CD8+ T cells and promote either T cell tolerance or full effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection – where HBV-specific naïve CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction – to identify a subset of KCs (referred to as KC2) that improves the antiviral function of T cells upon exogenous administration of IL-2. Mechanistically, KC2 were found to be both enriched in the IL-2 sensing machinery and poised to productively cross-present hepatocellular antigens in response to this cytokine. Removing MHC-I from all KCs – including KC2 – as well as selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. Together, these findings indicate that, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment and suggest new strategies for boosting T cell immunity in the liver.
2021-09-01 | GSE152211 | GEO
Project description:Liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) have important roles in liver homeostasis and host defense. Sharing the same microenvironment in the liver sinusoid, they form an effective scavenger cell system for removal of potentially harmful blood-borne substances. Unlike most other endothelia, LSECs are highly efficient in endocytosis of nanoparticles, including virus. Though controversial, LSECs have been reported to act as antigen presenting cells, thus contributing importantly to induction of immune tolerance in liver. There are also controversies about LSEC and KC specific markers, which may be due to overlapping cell functions, species differences, and/or problems with cell purification. We therefore used label-free proteomics to characterize and quantitatively compare proteome of freshly isolated, highly pure rat LSECs (SE-1/CD32b positive) and KCs (CD11b/c positive.We found that most immune genes expressed in KCs were also expressed in LSECs, albeit at a lower density, and they also have overlap in cell surface marker expression. Both cell types express high levels of scavenger receptors and immune lectins.
2020-11-11 | PXD012080 | Pride
Project description:Kupffer cells (KCs) self-renew by local proliferation in the adult independently from monocytes (Mos). However, how they maintain during chronic metabolic disorders such as non-alcoholic steatohepatitis (NASH) remains ill-defined. We characterized KCs during NASH and observed diversity in the KC pool, with a significant fraction of monocyte-derived KCs (MoKCs). Here, we aim to uncover the transcriptional landscapes of KCs subsets found in a mouse model of methionine and choline deficient (MCD)-diet induced non-alcoholic steatohepatitis (NASH).
2020-12-04 | GSE138778 | GEO
Project description:Background and aims: Patients with decompensated cirrhosis present serious infections of bacterial origin. During homeostasis, resident macrophages from the liver or Kupffer cells (KCS) play a key role in the phagocytosis of circulating bacteria. The objective of this study was to characterize the transcripomic and functional profile of KCs in liver cirrhosis and its relationship with the risk of infections. Methods: KCs were isolated from livers of patients with cirrhosis (n = 4) and controls (n = 5) and the profile was determined by RNA sequencing. The phenotype and altered molecular pathways of the isolated KCS were analyzed through GSEA . Results: The expression profile of KCs is specific and different depending on whether they reside in a cirrhotic or control liver. The GO analysis revealed that the pathways differentially expressed in KCs isolated from cirrhotic liver are implicated in the immune response. The GSEA showed that KCs isolated from patients with cirrhosis present a greater overexpression of M1 markers with respect to M2 (normalized enrichment score, NES: 1.68, p <0.01 vs. NES: 0.8, p <0.01). Conclusion: The KCS of patients with cirrhosis have a unique and distinct gene expression profile characterized by up-regulation of M1 markers.
2020-09-11 | GSE123661 | GEO
Project description:The cell-cell interaction between hepatocytes and Kupffer cells (KCs) is crucial for maintaining liver homeostasis, and the loss of KCs and hepatocytes is known to represent a common pathogenic phenomenon in autoimmune hepatitis. Until now, the mechanisms of cell-cell interaction between hepatocytes and KCs involved in immune-mediated hepatitis remains unclear. Here we dissected the impact of activated mTORC1 on the cell-cell interaction of KCs and hepatocyte in immune-mediated hepatitis. In the liver from patients with AIH and mice administrated with Con-A, mTORC1 was activated in both KCs and hepatocytes. The activated mTORC1 signal in hepatocytes with Con-A challenge caused a markedly production of miR-329-3p. Upregulated miR-329-3p inhibited SGMS1 expression in KCs through paracrine, resulting in the death of KCs. Most of maintained KCs were p-S6 positive and distributed in hepatocyte mTORC1 negative area. The activation of mTORC1 enabled KCs expressed complement factor B (CFB) to enhance the complement alternative system, which produced more complement factors to aggravate liver injury. Our findings remonstrate a heterogeneous role of mTORC1 in specific cell type for maintaining tolerogenic liver environment, and will form the basis for the development of new interventions against immune-mediated hepatitis.
2022-12-07 | GSE218700 | GEO
Project description:Aim: To find out the effects of small extracellular vesicles (sEVs) from short-term activated and long-term activated hepatic stellate cells (HSCs) on Kupffer cells (KCs) and bone marrow-derived monocytes (MOs). Methods: For the isolation of HSC-derived sEVs, culture media (CMs) from Day 0 to Day 3 and Day 7 to Day 14 were collected. The sEVs from Day 0 to Day 3 HSC CMs were referred to as short-term activated HSC-sEVs (3dHSC-sEVs), and those from Day 7 to Day 14 HSC CMs were referred to as long-term activated HSC-sEVs (14dHSC-sEVs). Purified primary rat KCs and MOs were cocultured with 3dHSC- or 14dHSC-sEVs for 48 h. HSC-sEVs cocultured KCs or MOs were lysed in TRIzol (Life Technologies) for RNA sample preparation at the indicated time points.
2024-08-29 | E-MTAB-12754 | biostudies-arrayexpress
Project description:Kupffer cells (KCs) are tissue-resident macrophages which colonize the liver early during embryogenesis. KCs start to acquire a tissue-specific transcriptional signature immediately after colonizing the liver, mature together with the tissue, and adapt to the tissue?s functions. Throughout development and adulthood, KCs have distinct core functions that are essential for liver and organismal homeostasis, such as supporting fetal erythropoiesis as well as postnatal erythrocyte recycling and liver metabolism. However, whether perturbations of macrophage core functions during development contribute to or cause disease at postnatal stages is poorly understood. Here, we utilize a mouse model of maternal obesity to perturb KC functions during gestation. We show that offspring exposed to maternal obesity develop fatty liver disease, driven by aberrant developmental programming of KCs that persists into adulthood. Programmed KCs mediate lipid uptake by hepatocytes through apolipoprotein secretion. KC depletion in neonates born to obese mothers, followed by replenishment with exogenous monocytes, rescues the fatty liver disease. The transcriptional programming of KCs and the fatty liver disease phenotype are also rescued by genetic depletion of hypoxia-inducible factor alpha (Hif1?) in macrophages during gestation. These results establish developmental perturbation of KC functions as a cause for the development of fatty liver disease in adult life and, thereby, place fetal-derived macrophages as intergenerational messengers within the concept of developmental origins of health and diseases.
2025-09-01 | PXD058285 | Pride