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A chemokine trail laid down by migratory dendritic cells directs antigen-presenting monocytes into draining lymph nodes

ABSTRACT: A chemokine trail laid down by migratory dendritic cells directs antigen-presenting monocytes into draining lymph nodes

PROVIDER: PRJNA889729 | ENA |

REPOSITORIES: ENA

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A chemokine trail laid down by migratory dendritic cells directs antigen-presenting monocytes into draining lymph nodes

Project description:Antigen presenting dendritic cells (DCs) and monocytes capture and transport antigens from barrier tissues for presentation to antigen-specific T cells in the draining-lymph nodes (LNs). While DCs enter LNs through afferent lymphatics in a CCR7-dependent manner, how exactly antigen-carrying monocytes reach LNs is less clear since monocytes do not express CCR7 and can also enter LNs via the bloodstream. In steady state, and following injection of several PAMPs, scRNA-seq data on LN mononuclear phagocytes identified LN resident versus migratory type 1 and type 2 conventional (c)DCs despite downregulation of DC subset-defining transcripts, such as Xcr1, Clec9a, H2-Ab1, Sirpa, and Clec10a on migratory cDCs. Migratory cDCs gained expression of transcripts controlling cellular migration such as Ccr7, Ccl17, Ccl22, and Ccl5, while migratory monocytes expressed Ccr5 without Ccr7. Using two tracking methods and a gating strategy that clearly distinguishes migratory CD88hiCD26lo monocytes from CD88-CD26hi cDCs, we found that both captured antigens in the lung and migrated to lung-draining LNs. Using global and mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, and Batf3-deficient mice, we found that CCR5+ monocytes follow CCL5-secreting migratory cDCs to reach the draining LN via lymphatic vessels. In a model of asthma, such recruited monocytes regulated the induction of type 2 immunity. Overall, our data suggest that CCL5-secreting migratory cDCs lay down the chemokine trail for CCR5+ antigen-presenting monocytes to reach draining lymph nodes and regulate adaptive immunity.

2022-10-17 | GSE215299 | GEO

Analysis of classical and migratory DC from the skin draining LNs of Flt3L treated mice and comparison to LPS treated DC from skin draining LN and peritoneal macrophages

Project description:Analysis of the differential transcriptome of DC derived from tissue vs. LN origin. The overall hypothesis is these data would reveal how migratory DC may be differently programmed from classical DC and might also suggest difference within migratory DC subsets relating to function. RNA obtained from migratory DC subsets and classical CD8a DC isolated by flow cytometry sorting from skin draining LNs of Flt3L treated mice or LPS treated mice

2014-08-01 | E-GEOD-53588 | biostudies-arrayexpress

Cytokine and receptor expression in skin draining lymph nodes after skin immunization

Project description:Topical (epicutaneous, e.c.) application of the adjuvant CpG ODN during immunization leads to a robust immune response compared to when subcutaneous (s.c.) administration. Dendritic cells are hematopoietically derived cells that are important in cross-presenting to and activating CD8 T cells. Dermal dendritic cells are one of the two major dendritic cell subsets found in the skin which mobilize from the skin to draining lymph nodes to present to T cells upon activation. Dermal dendritic cells are found in skin draining lymph nodes around 24 hours post immunization. To determine how the immune system respond differently between e.c. versus s.c. administration of CpG ODN, we evaluated changes in the skin draining lymph node environment upon the two routes of adjuvant application. Expression chemokines and chemokine receptors were assessed with real-time qPCR. To determine the changes in the skin draining lymph node environment (cytokine and cytokine receptor levels) upon immunization via real time RT-PCR.

2019-06-28 | GSE133438 | GEO

microRNA expression of TRAIL-sensitive and TRAIL-resistant Bel-7402 cells

Project description:To further analyze the change of microRNA (miRNA) between TRAIL-sensitive and TRAIL-resistant Bel-7402 cells Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

2015-10-20 | GSE74130 | GEO

TRAIL expressing monocyte/macrophages reduce inflammation and attenuate atherosclerosis

Project description:Circulating TRAIL is reduced in cardiovascular disease patients and TRAIL deletion in mice exacerbates disease. The source of TRAIL and protective mechanism(s) are unclear. Monocyte TRAIL mRNA was reduced from coronary artery disease patients, strikingly associating with reduced plasma TRAIL. A strong inverse correlation between plasma TRAIL and IL-18 was observed, with IL-18 repressing monocyte TRAIL mRNA. In mice, two sources were investigated using bone-marrow (BM) transplants; TRAIL expressed only in BM (BM-TRAIL) or everywhere except BM (parenchymal-TRAIL), vs. whole-body TRAIL ablation (null-TRAIL). BM-TRAIL attenuated macrophage content and atherosclerosis. BM-derived macrophages with TRAIL deletion were more inflammatory, with impaired migration and reduced expression of cholesterol efflux, efferocytosis and nitric oxide-controlling genes. TRAIL expression also reduced islet macrophage content, but only parenchymal-TRAIL islets had improved function. Recombinant TRAIL administration stimulated insulin expression and islet mass. We propose TRAIL maintains monocyte/macrophage homeostasis and limits the progression of atherosclerosis and islet dysfunction.

2019-12-03 | GSE107645 | GEO

Comparison of Trail+/+ versus Trail-/- splenic NK cells from naïve and LCMV-infected mice

Project description:Investigation of the change of the Trail-dependent NK cell transcriptome during short-term (24h) infection with lymphocytic choriomeningitis virus (LCMV). RNA sequencing-based transcriptomics analysis was performed in spleen-isolated (NK1.1+CD3-) NK cells from 3 naïve Trail+/+ mice, 3 naive Trail-/- mice, 4 LCMV-infected Trail+/+ mice, and 4 LCMV-infected Trail-/- mice.

2019-08-27 | E-MTAB-7562 | biostudies-arrayexpress

Transcription profiling of human TRAIL-resistant metastatic vs primary TRAIL-sensitive melanoma cells

Project description:T1 and G1 are the two melanoma cell lines, established from primary tumor (T1) and lymph node metastases (G1) of a 77 years old male patient. While G1 cells were resistant to TRAIL (TNF-related apoptosis-inducing ligand) mediated cell death, T1 cells exhibited a high dose- and time-dependent sensitivity to TRAIL. Cells were treated with or without of two doses (0.2 and 1ug/ml) of TRAIL for 24 h. Gene expression of each sample vs pool was measured. TRAIL-resistant metastatic G1 vs primary TRAIL-sensitive T1 was compared.

2006-01-01 | E-MEXP-247 | biostudies-arrayexpress

Analysis of classical and migratory DC from the skin draining LNs of Flt3L treated mice and comparison to LPS treated DC from skin draining LN and peritoneal macrophages

2014-08-01 | GSE53588 | GEO

single cell RNA sequencing of migratory dendritic cells after intranasal adjuvant/tolerogen administration

Project description:We compared migratory DCs in draining mediastinal lymph node after intranasal administration of different vaccine adjuvants based on CTA1 subunit of cholera toxin. The goal was to determine different characteristics of dendritic cells subsets after pro-inflammatory vs tolerogenic adjuvant. We had 3 groups: CTA1-DD (pro- inflammatory), CTA1(R7K)-DD (tolerogenic) and PBS to define DC which migrate to LN. All vaccine constructs included 3Ea peptide to allow for sorting of DC which took up the vaccine.

2023-05-15 | E-MTAB-12942 | biostudies-arrayexpress

Proteomic analysis of TRAIL-induced endogenous RIPK3-dependent necrosome complex

Project description:Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a well-known inducer of apoptosis via formation of the primary death-inducing signaling complex (TRAIL-DISC) at the level of membrane death receptors (DR4 and DR5) which recruit successively FADD and caspase-8. TRAIL can also induce necroptosis when caspases are inhibited. Necroptosis is a regulated cell death dependent on the formation of a cytosolic necrosome complex which includes RIPK1, RIPK3 and MLKL proteins. Elucidating the molecular mechanisms involved in TRAIL-induced necroptosis might provide new insights into the TRAIL death signaling pathway. Here, we report the analysis by mass spectrometry of endogenous RIPK3-dependent necrosome complex constituents upon necroptosis induced by TRAIL/z-VAD/Birinapant (TzB) in HT29 cells. Besides characterization of RIPK1, RIPK3, MLKL, FADD, caspase-8, we find TRIM21 as a new constituent of the necrosome complex. Moreover RIPK1, RIPK3, MLKL, P-MLKL, FADD, caspase-8 and TRIM21 are also found associated to the native TRAIL-DISC upon TzB stimulation showing initiation of the necrotic pathway at the level of TRAIL death receptors in HT29 cells. Finally, TRIM21 may positively modulate necroptosis induction by downregulating NF-kB activation.

2021-03-18 | PXD003383 | Pride

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