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Defining DC response to cognate T cell interaction in the antigen-challenged lymph node [dataset 3]

ABSTRACT: Defining DC response to cognate T cell interaction in the antigen-challenged lymph node [dataset 3]

PROVIDER: PRJNA530542 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8836840.fastq.gz	Fastqsanger.gz
	SRR8836850.fastq.gz	Fastqsanger.gz
	SRR8836860.fastq.gz	Fastqsanger.gz
	SRR8836870.fastq.gz	Fastqsanger.gz
	SRR8836841.fastq.gz	Fastqsanger.gz

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Defining DC response to cognate T cell interaction in the antigen-challenged lymph node [dataset 3]

Project description:We designed an experimental set up to probe DC responses to cognate T cell encounter in antigen draining LN

2019-04-03 | GSE129213 | GEO

DC Respond to Cognate T Cell Interaction in the Antigen-Challenged Lymph Node.

Project description:Dendritic cells (DC) are unrivaled in their potential to prime naive T cells by presenting antigen and providing costimulation. DC are furthermore believed to decode antigen context by virtue of pattern recognition receptors and to polarize T cells through cytokine secretion toward distinct effector functions. Diverse polarized T helper (TH) cells have been explored in great detail. In contrast, studies of instructing DC have to date largely been restricted to in vitro settings or adoptively transferred DC. Here we report efforts to unravel the DC response to cognate T cell encounter in antigen-challenged lymph nodes (LN). Mice engrafted with antigen-specific T cells were immunized with nanoparticles (NP) entrapping adjuvants and absorbed with antigen to study the immediate DC response to T cell encounter using bulk and single cell RNA-seq profiling. NP induced robust antigen-specific TH1 cell responses with minimal bystander activation. Fluorescent-labeled NP allowed identification of antigen-carrying DC and focus on transcriptional changes in DC that encounter T cells. Our results support the existence of a bi-directional crosstalk between DC and T cells that promotes TH1 responses, including involvement of the ubiquitin-like molecule Isg15 that merits further study.

| S-EPMC6496461 | biostudies-literature

Cognate T cell interactions affect the DC transcriptome [dataset 4]

Project description:Cognate T cell interactions affect the DC transcriptome [dataset 4]

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Cognate T cell interactions affect the DC transcriptome [dataset 4]

Project description:Our data suggest that peptide-presenting DC receive signals from synapse-forming antigen specific CD4+ or CD8+ T cells that alter the DC expression profile. To further test this notion, we hock immunized T cell-engrafted mice with NP harboring CpG and coated with OVA (OVA / CpG NP) or the control antigen BSA (BSA / CpG NP) and isolated NP+ DC for RNAseq.

2019-04-03 | GSE129214 | GEO

Human melanoma-derived extracellular vesicles reprogram dendritic cells potentially enabling lymph node metastases

Project description:Evolution of melanoma from a primary tumor to widespread metastasis is crucially dependent on lymphatic spread. The mechanisms regulating the initial step in metastatic dissemination via regional lymph nodes remain largely unknown. We have previously described a dysfunctional immune profile that precedes evidence of metastasis in the first node draining from the primary tumor, the sentinel lymph node (SLN). Herein, we explore the role of melanoma-derived extracellular vesicles (EVs) as mediators of this pre-metastatic niche through cargo-specific polarization of dendritic cells (DCs). Utilizing mass cytometry, pre-metastatic SLNs demonstrate compromised co-stimulatory CD80 expression compared to healthy lymph nodes. Similarly, DCs matured in vitro in the presence of melanoma EVs showed impaired co-stimulation and polarization towards a chronic inflammatory cytokine milieu. Profiling of melanoma EV cargo identified shared proteomic and RNA signatures including the signaling axis S100A8, S100A9 and cognate receptor TLR4. Mechanistically, S100A8 and S100A9 compromised DC maturation, a phenotype which was partially recovered following TLR4 blockade. Early evidence demonstrates similar EVs can be isolated from human afferent lymphatic fluid ex vivo. Taken together, we propose synergistic interactions among melanoma EV cargo are responsible for suppressing DC maturation, potentially explaining the survival of malignant melanocytes metastasizing into seemingly “normal” regional lymph nodes.

2018-10-26 | PXD005539 | Pride

Armatimonadetes bacterium DC isolate:DC

Project description:Armatimonadetes bacterium DC isolate:DC Genome sequencing and assembly

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Novel splenic DC

Project description:Novel splenic DC

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T cell zone resident macrophages silently dispose of apoptotic cells in the lymph node

Project description:Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system. In lymph nodes (LN), they are also believed to dispose of apoptotic cells, a critical function usually achieved by macrophages (Mφ) in other tissues. We report a population of tolerogenic Mφ located in the T cell zone of LN. T zone Mφ (TZM) are long lived Mφ seeded after birth and slowly replaced by blood monocytes. We show that TZM but not DC act as the only professional scavengers clearing apoptotic cells in the LN T cell zone. Importantly, we demonstrate that TZM prevent the capture of apoptotic cells by DC and the associated potential noxious activation of T cell immunity. We thus propose a new model in which efferocytosis and T cell activation are uncoupled processes handled by TZM and DC respectively.

2017-08-21 | GSE93592 | GEO

Defining the incidence and clinical significance of lymph node metastasis in soft tissue sarcoma.

Project description:IntroductionThe incidence and clinical significance of lymph node metastasis (LNM, N1) in soft tissue sarcoma (STS) is unclear. Recent studies have focused on extremity/trunk STS (ETSTS). We sought to define the subgroup of patients with LNM at sarcoma diagnosis across all disease sites and histologies.MethodsWe identified and categorized 89,870 STS patients from the National Cancer Data Base (1998-2012) by nodal stage. Pathologically confirmed LNM (pN1) were identified in 1404 patients; 1750 had clinically suspicious but not pathologically confirmed LNM (cN1). Survival analyses were performed by Kaplan-Meier method.ResultsOf 3154 patients (3.5%) with pN1 or cN1 LNM at presentation, 1310 had synchronous distant metastasis (M1). LNM affected a small proportion of patients (5.8% head/neck, 5.3% intrathoracic, 5.1% intra-abdominal, 2.0% ETSTS). Angiosarcoma (6%), epithelioid (13%), clear cell (16%), and small cell sarcoma (19%) had the highest incidence of LNM, although liposarcoma, fibrous histiocytoma, and leiomyosarcoma accounted for the greatest number of LNM patients. For pN1M0 disease, median overall survival (OS) was 28.2 months, varying by histology. Among patients with pN1M0 STS, angiosarcoma, clear cell sarcoma, leiomyosarcoma, and fibrous histiocytoma were associated with worse median OS (19.4, 23.8, 27.1, and 29.3 months) compared to epithelioid sarcoma and liposarcoma (49.6 and 56.0 months, p < 0.001).ConclusionDespite clinical suspicion, pathologic LN evaluation in STS is inconsistently performed. LNM occurs across anatomic disease sites and is unevenly distributed across histologies. Although M1 disease portends poor prognosis regardless of LN status, LNM predicts worse OS in a histology-dependent manner in M0 disease.

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Vitamin A treatment rescues neonatal infection-induced durably impaired lymph node function (RNA-Seq DC)

Project description:Vitamin A treatment rescues neonatal infection-induced durably impaired lymph node function (RNA-Seq DC)

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