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Donor non-classical monocytes recruit recipient classical monocytes from the spleen by activating donor alveolar macrophages

ABSTRACT: Donor non-classical monocytes recruit recipient classical monocytes from the spleen by activating donor alveolar macrophages

PROVIDER: PRJNA701602 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13697035.fastq.gz	Fastqsanger.gz
	SRR13697036.fastq.gz	Fastqsanger.gz
	SRR13697037.fastq.gz	Fastqsanger.gz
	SRR13697038.fastq.gz	Fastqsanger.gz

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Similar Datasets

Donor non-classical monocytes recruit recipient classical monocytes from the spleen by activating donor alveolar macrophages

Project description:Primary Graft Dysfunction (PGD) is the predominant cause of early graft loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular non-classical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical monocytes (CM) are mobilized from the spleen and, upon entry into the allograft, permeabilize the vascular endothelium to allow neutrophil extravasation necessary for PGD. Here, we show that CCL2-CCR2 axis is necessary for CM recruitment. Surprisingly, although intravital imaging and multichannel flow cytometry revealed that pharmacological or genetic depletion of donor NCM abrogated CM recruitment, single-cell RNAseq identified donor alveolar macrophages (AM) as predominant CCL2 secretors. Unbiased transcriptomic analysis of human and murine tissues combined with murine knockouts and chimeras indicated that while IL1β was secreted by multiple cell lineages, donor NCM were responsible for the early activation of AM and CCL2 release. IL1β production by NCM was NLRP3 inflammasome-dependent and inhibited by donor treatment using a clinically approved sulphonylurea, Glyburide. Production of CCL2 in the donor AM occurred through IL1R-dependent activation of PKC and NFκB-pathway. Accordingly, we show that IL1β-dependent paracrine interaction between donor NCM and AM leads to recruitment of host AM necessary for PGD. Since depletion of donor NCM, IL1β or IL1R antagonism, and inflammasome inhibition, abrogated recruitment of CM as well as PGD and are feasible using FDA-approved compounds, our findings have potential for immediate clinical translation.

2024-02-01 | GSE166679 | GEO

Comprehensive cell surface proteomics defines markers of classical, intermediate and non-classical monocytes

Project description:Monocytes are a critical component of the cellular innate immune system, and can be subdivided into classical, intermediate and non-classical subsets on the basis of surface CD14 and CD16 expression. Classical monocytes play the canonical role of phagocytosis, and account for the majority of circulating cells. Intermediate and non-classical cells are known to exhibit varying levels of phagocytosis and cytokine secretion, and are differentially expanded in certain pathological states. Characterisation of cell surface proteins expressed by each subset is informative not only to improve understanding of phenotype, but also to provide biological insight into function. Here we use highly multiplexed Tandem-Mass-Tag (TMT)-based mass spectrometry with selective cell surface biotinylation to characterise the classical monocyte surface proteome, then interrogate the phenotypic differences between each monocyte subset to identify novel protein markers.

2020-03-03 | PXD013832 | Pride

Donor pulmonary intravascular nonclassical monocytes recruit recipient neutrophils and mediate primary lung allograft dysfunction.

Project description:Primary graft dysfunction is the predominant driver of mortality and graft loss after lung transplantation. Recruitment of neutrophils as a result of ischemia-reperfusion injury is thought to cause primary graft dysfunction; however, the mechanisms that regulate neutrophil influx into the injured lung are incompletely understood. We found that donor-derived intravascular nonclassical monocytes (NCMs) are retained in human and murine donor lungs used in transplantation and can be visualized at sites of endothelial injury after reperfusion. When NCMs in the donor lungs were depleted, either pharmacologically or genetically, neutrophil influx and lung graft injury were attenuated in both allogeneic and syngeneic models. Similar protection was observed when the patrolling function of donor NCMs was impaired by deletion of the fractalkine receptor CX3CR1. Unbiased transcriptomic profiling revealed up-regulation of MyD88 pathway genes and a key neutrophil chemoattractant, CXCL2, in donor-derived NCMs after reperfusion. Reconstitution of NCM-depleted donor lungs with wild-type but not MyD88-deficient NCMs rescued neutrophil migration. Donor NCMs, through MyD88 signaling, were responsible for CXCL2 production in the allograft and neutralization of CXCL2 attenuated neutrophil influx. These findings suggest that therapies to deplete or inhibit NCMs in donor lung might ameliorate primary graft dysfunction with minimal toxicity to the recipient.

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Gene expression of donor monocytes recovered from various tissues of recipient mice one day after transfer

Project description:Gene expression of donor monocytes recovered from various tissues of recipient mice one day after transfer

| PRJNA548331 | ENA

Gene expression of donor monocytes recovered from various tissues of recipient mice one day after transfer

Project description:Monocyte are recruited to almost all peripheral tissues. Micro-environmental stimuli appeared to alter monocyte transcription once they enter the intestine and their subsequent development in the tissue. We therefore investigated whether there is tissue specific monocyte adaption and differentiation in vivo by examining donor monocytes in various tissues i.e. small intestine, liver, spleen and BM.

2019-06-12 | GSE132537 | GEO

Single Cell Transcriptional Analysis of Donor and Recipient Immune Cell Chimerism in the Rejecting Kidney Transplant

Project description:We analyzed the transcriptomes from 81139 cells from 5 kidney transplant biopsies. We sequenced the germline coding sequence from donor and recipient pairs corresponding to each biopsy as a reference to determine donor host chimerism in each kidney.

2020-07-22 | GSE145927 | GEO

Diagnosing recipient- vs. donor-derived posttransplant myelodysplastic neoplasm via targeted single-cell mutational profiling

Project description:Targeted genotyping-based identification of donor- and recipient-derived cells to resolve the origin of myelodysplastic syndrome (MDS) following allogeneic stem cell transplantation in the context of aplastic anemia (AA).

2024-12-06 | GSE228278 | GEO

Predicting Acute Cardiac Allograft Rejection Using Donor and Recipient Gene Expression

Project description:Acute rejection in cardiac transplant patients is still a contributing factor to limited survival of the implanted heart. Currently there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplantation acute rejection, which would be of great importance for personalizing immunosuppressive treatment. Within the Biomarkers in Transplantation initiative, the predictive biomarker discovery focused on data and samples collected before or during transplantation such as: clinical variables, genes and proteins from the recipient, and genes from the donor. Based on this study, the best predictive biomarker panel contains genes from the recipient whole blood and from donor endomyocardial tissue and has an estimated area under the curve of 0.90. This biomarker panel provides clinically relevant prediction power and may help personalize immunosuppressive treatment and frequency of rejection monitoring.

2017-09-29 | GSE33970 | GEO

Gene expression profiles of T cell fraction enriched for donor antigen-reactive T cells in skin allografted recipient mice

Project description:This SuperSeries is composed of the following subset Series: GSE32952: Gene expression profiles of T cell fraction enriched for donor antigen-reactive T cells in skin allografted recipient mice (I) GSE32953: Gene expression profiles of T cell fraction enriched for donor antigen-reactive T cells in skin allografted recipient mice (II) Refer to individual Series

2011-10-12 | E-GEOD-32955 | biostudies-arrayexpress

Tracking of donor and recipient immune and leukemia phenotypes after allogeneic stem cell transplantation using mitochondrial DNA mutations. [Tapestri]

Project description:Mitochondrial DNA mutations (mtDNA) enable deconvolution of donor- and recipient-derived single cell profiles. Here, we provide examples for sensitive donor-recipient deconvolution of peripheral blood and bone marrow ASAP-seq profiles in the context of incipient and overt AML relapse following allogeneic hematopoietic stem cell transplantation. Further, using single cell DNA sequencing (Tapestri), we demonstrate co-evolution of mtDNA and somatic nuclear DNA mutations in relapsed CLL post-HSCT.

2024-08-31 | GSE234556 | GEO

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