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Lymphoid tissue specific homing of bone marrow-derived dendritic cells

ABSTRACT: Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer. This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE15784 | GEO | 2009/04/23

SECONDARY ACCESSION(S): PRJNA116859

REPOSITORIES: GEO

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Lymphoid tissue specific homing of bone marrow-derived dendritic cells

Project description:Because of their potent immunoregulatory capacity, dendritic cells (DCs) have been exploited as therapeutic tools to boost immune responses against tumors or pathogens, or dampen autoimmune or allergic responses. Murine bone marrow-derived DCs (BM-DCs) are the closest known equivalent of the blood monocyte-derived DCs that have been used for human therapy. Current imaging methods have proven unable to properly address the migration of injected DCs to small and deep tissues in mice and humans. This study presents the first extensive analysis of BM-DC homing to lymph nodes (and other selected tissues) after intravenous and intraperitoneal inoculation. Following intravenous delivery, DCs accumulated in the spleen, and preferentially in the pancreatic and lung-draining lymph nodes. In contrast, DCs injected intraperitoneally were found predominantly in peritoneal lymph nodes (pancreatic in particular), and in omentum-associated lymphoid tissue. This uneven distribution of BM-DCs, independent of the mouse strain and also observed within pancreatic lymph nodes, resulted in the uneven induction of an immune response in different lymphoid tissues. These data have important implications for the design of systemic cellular therapy with DCs, and in particular underlie a previously unsuspected potential for specific treatment of diseases such as autoimmune diabetes and pancreatic cancer. This SuperSeries is composed of the following subset Series: GSE15748: Gene expression in PLN vs. ILN or MLN in mice GSE15753: Gene expression in GLN versus PDLN in NOD mice Refer to individual Series

2009-04-23 | E-GEOD-15784 | biostudies-arrayexpress

IL-12 From Endogenous cDC1, and Not Vaccine DC, Is Required for Th1 Induction

Project description:In this study, we generated a chimeric situation by injection of different gene-modified BM-DCs into different strains of gene-modified recipient mice. This allowed us to identify the separate functional contributions of injected versus endogenous DCs for Th1 polarization. We identified the cellular source of IL-12p70 production after subcutaneous BM-DC vaccination as endogenous migratory XCR1+ bystander DCs in the skin draining lymph nodes. DC-DC and DCT cell interaction studies revealed a time course of Th0 priming by injected BM-DCs, followed by interactions of BM-DC with the IL-12+ XCR1+ bystander DCs, and finally IL-12+ XCR1+ bystander DC interactions for Th1 induction. Transcriptional profiling of the bystander DCs underscores their Th1 polarization potential. Together, this study shows that DC-vaccination requires the bystander activation of endogenous DCs for Th1 priming. Our data also challenge the general concept of Th1 priming by a single DC providing all signals 1, 2 and 3 to T cells for Th1 polarization.

2020-06-02 | GSE124677 | GEO

Gene expression in GLN versus PDLN in NOD mice

2009-04-23 | GSE15753 | GEO

Gene expression of murine DCs from bone marrow and spleen

Project description:Next to driving hematopoiesis, the bone marrow (BM) also serves as a secondary lymphoid organ, as it can drive T cell priming by resident dendritic cells (DC). When analyzing these DCs in murine BM, we uncovered that they are localized around sinusoids, can (cross)-present antigens, become activated upon intravenous LPS-injection, and for the majority belong to the cDC2 subtype which is associated with Th2/Th17 immunity. Gene-expression profiling revealed that BM-resident DCs are enriched for several c-type lectins, including Dectin-1, which can bind beta-glucans expressed on fungi and yeast. Indeed, DCs in BM were much more efficient in phagocytosis of both yeast-derived zymosan-particles and Aspergillus than their splenic counterparts, which was highly dependent on Dectin-1. DCs in human BM could also phagocytose zymosan, which was dependent on β1-integrins. Moreover, zymosan-stimulated BM-resident DCs enhanced the differentiation of hematopoietic stem and progenitor cells towards neutrophils, while also boosting the maintenance of these progenitors. Our findings signify an important role for BM DCs as translators between infection and hematopoiesis, in particular in anti-fungal immunity. The ability of BM-resident DCs to boost granulopoiesis is relevant from a clinical perspective, and contributes to our understanding of the increased susceptibility for fungal infections following BM damage.

2021-08-31 | GSE182984 | GEO

scATAC-seq of innate immune cells from mice treated with the adjuvant 3M052

Project description:Purpose: to explore the epigenomic landscape of innate immune cells stimulated with a novel adjuvant, 3M052 Methods: Mice were injected with 3M052. Draining lymph nodes were negatively selected for CD19+ and CD3+, then flow sorted into four populations: Dendritic cells (DCs), Double positive cells (DP, CD11b+BST1+), Ly6c+ cells (Ly6c), and plasmacytoid dendritic cells (pDCs). Lymph nodes were harvested at baseline (D0), 24 hours post-treatment (D1) or 28 days post-treatment (D28).

2021-12-05 | GSE180752 | GEO

Transcriptional profile of IL33 & PD1-treated ILC2 from KPC tumor-bearing mice

Project description:We investigated the genetic profiles of IL33 and PD1-treated group 2 innate lymphoid cells (ILC2) harvested from KPC tumors and draining lymph nodes in a pancreatic ductal adenocarcinoma (PDAC) mouse model.

2019-09-03 | GSE136720 | GEO

Gene expression in GLN versus PDLN in NOD mice

Project description:Comparison of the gene expression in the two pancreatic lymph nodes: gastric lymph node (GLN) and pancreatico-duodenal lymph node (PDLN) in NOD mice. The analysis was done in an attempt to explain the preferential homing of bone marrow-derived dendritic cells to the GLN after intravenous injection. GLN and PDLN were excised from 4 individual 12-wk old female NOD mice and RNA was extracted after tissue homogenization in Trizol for processing onto microarray (Agilent 4x44K). Each array corresponds to one single mouse, thus this study comprise 4 biological replicates.

2010-04-08 | E-GEOD-15753 | biostudies-arrayexpress

Genome-Wide Gene Expression Profiles in the Pancreatic Lymph Nodes of At-Risk Autoantibody Positive Individuals

Project description:Type 1 diabetes (T1D) is a polygenic autoimmune disorder caused by autoreactive T cells that recognize pancreatic islet antigens and subsequently destroy insulin-producing β-cells. Pancreatic lymph nodes (PLN) are an essential site for the development of T1D, where tolerance to pancreatic self-antigens is first broken and the autoimmune responses are amplified. The purpose of this study was to identify candidate genes and pathways in the PLN that may contribute to the pathogenesis of T1D. Microarray analysis was performed on the PLN of human non-diabetic healthy controls (n=7) and at-risk autoantibody-positive subjects (n=13).

2015-03-03 | E-GEOD-66413 | biostudies-arrayexpress

Immune crosstalk between pancreas, gut and liver through lymph node sharing [scRNA-seq]

Project description:To investigate tissue of origin effects on migratory dendritic cell (DC) gene expression in shared lymph nodes we performed bulk RNAseq of DCs from each tissue (liver, pancreas, duodenum). We then performed single cell sequencing of the DCs within the draining lymph nodes.

2022-07-27 | GSE209702 | GEO

Immune crosstalk between pancreas, gut and liver through lymph node sharing [bulk RNA-seq]

2022-07-27 | GSE209701 | GEO

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