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Lung Megakaryocytes are Immune Modulatory Cells

ABSTRACT: Lung Megakaryocytes are Immune Modulatory Cells

PROVIDER: PRJNA664993 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12692675.fastq.gz	Fastqsanger.gz
	SRR12692676.fastq.gz	Fastqsanger.gz
	SRR12692677.fastq.gz	Fastqsanger.gz
	SRR12692678.fastq.gz	Fastqsanger.gz
	SRR12692679.fastq.gz	Fastqsanger.gz

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Lung Megakaryocytes are Immune Modulatory Cells

Project description:Our data demonstrate that lung and bone marrow-derived megakaryocytes (Mks) have distinct immune phenotypes and functions; lung Mks secrete inflammatory cytokines and express molecules that are similar to many tissue resident leukocytes and antigen presenting cells (APCs), and lung Mks process live intact bacteria and present bacteria-derived antigen to CD4+ T cells both in vitro and in vivo. Our in vivo data suggest that lung Mks have important roles in the early activation of T cell responses to a pulmonary pathogen challenge, identifying a novel immune regulatory role for lung Mks.

2020-11-26 | GSE158358 | GEO

Lung megakaryocytes are immune modulatory cells.

Project description:Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megakaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow-resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term MkL, had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an MkL-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II-dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.

| S-EPMC7773372 | biostudies-literature

Extracellular vesicles of the Gram-positive gut symbiont Bifidobacterium longum induce immune-modulatory, anti-inflammatory effects

Project description:Extracellular vesicles of the Gram-positive gut symbiont Bifidobacterium longum induce immune-modulatory, anti-inflammatory effects

2023-04-30 | PXD038667 | Pride

Single Cell Transcriptomic Analysis of Lung and Hematopoietic Megakaryocytes from Embryonic and Adult Mice.

Project description:To create a transcriptomic library that spans multiple stages and sites of megakaryocyte development, scRNA-Seq was performed on cells isolated from embryonic day 13 fetal liver and lung, as well as week 10 adult bone marrow and lung. Enrichment of megakaryocytes in all tissues was accomplished using flow cytometry to sort for live-CD41+ cells. Only the top 1% of CD41+ events were captured in order to further enhance enrichment of megakaryocyte-lineage cells.

2021-01-04 | GSE152574 | GEO

Immune cells surveil aberrantly sialylated O-glycans on megakaryocytes to regulate platelet count

Project description:Immune cells surveil aberrantly sialylated O-glycans on megakaryocytes to regulate platelet count

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Gene expression profiles of cultured megakaryocytes

Project description:Cells obtained from adipose tissue are able to differentiate into megakaryocytes. We compared the gene expression profile of human adipose tissue derived megakaryocytes with that of megakaryocytes differentiated from human CD34 positive cord blood hematopoietic stem cells.

2021-04-05 | GSE112820 | GEO

Plasmacytoid dendritic cells regulate tissue homeostasis of megakaryocytes

Project description:Platelet homeostasis is essential for vascular integrity and immune defense. While the process of platelet formation by fragmenting megakaryocytes (thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of megakaryocytes (MKs) by their progenitor cells (megakaryopoiesis) remains unclear. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFN- to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This fine-tuned coordination between thrombopoiesis and megakaryopoiesis is crucial for MK and platelet homeostasis in steady state and stress. However, excessive activation of pDCs, such as by viral infections, can disturb this homeostatic circuit. Accordingly, we show that pDCs activated by SARS-CoV2 drive inappropriate megakaryopoiesis. Together, we uncover a hitherto unknown pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain tissue homeostasis of the megakaryocytic lineage.

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Immune cells surveil aberrantly sialylated O-glycans on megakaryocytes to regulate platelet count

Project description:Immune thrombocytopenia (ITP) is a common platelet disorder in pediatric patients. Pediatric and adult ITP have been associated with sialic acid alterations, but the pathophysiology of ITP remains elusive, and ITP is often a diagnosis of exclusion. Our analysis of pediatric ITP plasma samples showed increased anti-Thomsen-Friedenreich antigen (TF-antigen) antibody representation, suggesting increased exposure of the typically sialylated and cryptic TF-antigen in these patients. The O-glycan sialyltransferase St3gal1 add sialic acid specifically on the TF-antigen. To understand if TF-antigen exposure associates with thrombocytopenia, we generated a mouse model with targeted deletion of St3gal1 in megakaryocytes (MK) (St3gal1MK-/-). TF-antigen exposure was restricted to MKs and resulted in thrombocytopenia. Deletion of Jak3 in St3gal1MK-/- mice normalized platelet counts implicating involvement of immune cells. Interferon-producing Siglec H-positive bone marrow (BM) immune cells engaged with O-glycan sialic acid moieties to regulate type I interferon (IFN-I) secretion and platelet release (thrombopoiesis), as evidenced by partially normalized platelet count following and inhibition of interferon and Siglec H receptors. Single cell RNAseq determined that TF-antigen exposure by MKs primed St3gal1MK-/- BM immune cells to release IFN-I. Single cell RNAseq further revealed a new population of immune cells with a plasmacytoid dendritic cell (pDC)-like signature and concomitant upregulation of immunoglobulin re-arrangement gene transcripts Igkc and Ighm, suggesting additional immune regulatory mechanisms. Thus, aberrant TF-antigen moieties, often found in pathological conditions, regulate immune cells and thrombopoiesis in the BM, leading to reduced platelet count.

2021-06-29 | GSE179067 | GEO

Immune cells direct epithelial maturation during early human lung development

Project description:The adult human lung harbours a significant proportion of immune cells, which are known to play a crucial role in both normal lung homeostasis and pathogenesis. In this work, we collected CD45-enriched human lung cells from 6 to 22 week post conception (pcw) and built a single-cell transcriptome and proteome atlas. We showed a biphasic mode of immune cell development peaking at 8-9 and 20 pcw respectively. The developing immune cells potentially modulate the maturation of the epithelium through signalling molecules. We demonstrated using the lung organoid model that IL-1ß was required for epithelium differentiation. Overall, we provide a resource for the community of lung biologists and immunologists and provide insights on the interaction between the innate immune system and epithelium during fetal development.

2022-12-09 | E-MTAB-11528 | biostudies-arrayexpress

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