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Heterogeneity of LN resident macrophage

ABSTRACT: LN resident macrophages lining the lymphatic sinuses play critical roles in antigen capture and presentation as well as degradation. We used microarray to examine global gene expression profiles to compare SCS and med macrophages to determine the underlying molecular basis of their differential handling of antigens. Primary SCS and med macrophages were isolated and purified from LNs by flourescence-activated cell sorting and RNA extracted, amplified and hybridized for Affymetrix analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Tri Phan

PROVIDER: E-GEOD-15767 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation.

Phan Tri Giang TG Green Jesse A JA Gray Elizabeth E EE Xu Ying Y Cyster Jason G JG

Nature immunology 20090607 7

Subcapsular sinus (SCS) macrophages capture antigens from lymph and present them intact for B cell encounter and follicular delivery. However, the properties of SCS macrophages are poorly defined. Here we show SCS macrophage development depended on lymphotoxin-alpha1beta2, and the cells had low lysosomal enzyme expression and retained opsonized antigens on their surface. Intravital imaging revealed immune complexes moving along macrophage processes into the follicle. Moreover, noncognate B cells ...[more]

PMID: 19503106

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Heterogeneity of LN resident macrophage

Project description:LN resident macrophages lining the lymphatic sinuses play critical roles in antigen capture and presentation as well as degradation. We used microarray to examine global gene expression profiles to compare SCS and med macrophages to determine the underlying molecular basis of their differential handling of antigens.

2009-06-05 | GSE15767 | GEO

Expression data from CD4+ and CD11c+ cells from DO11.10 RAG2-/- mice

Project description:Abatacept is a recombinant CTLA-4 moleculed fused to a mutated human IgG molecule, which is clinically used in rheumatoid arthritis by inhibiting CD28-costimulation. This study aimed to inverstigate the ability of abatacept -mediated costimulation blockade to induce antigen-specific tolerance during primary immune responses. This is important as some studies have suggested that costimulation blockade can lead to CD4+ T cell anergy which could be beneficial for early therapy of autoimmune diseases such as rheumatoid arthritis. In addition we also investigated the effect that abatacept has on CD11c+ antigen presenting cells. This is important as costimulation blocakde can affect the biderectional interaction between CD4+ T cells and CD11c+ cells influencing the immunological outcome. We used microarrays to identify if abatacept treatment leads to antigen specific anergy using transgenic animals and models of priming and oral tolerance that established a synchronised monoclonal response. In addition this magnified the effect on the CD11c+ antigen presenting cells. This study included 5 experimental groups. DO11.10 RAG2-/- mice have CD4+ T cells specific for the ovalbumin (OVA) peptide OVA323-339. These mice were immunised with CFA/OVA s.c. (primed group) or tolerised by feeding with OVA (50mg/kg) in the drinking water. CD4+ cells were isolated 10 days post immunisation from draining lymph nodes (LNs) of unimmunised (pooled LNs and Spleen), orally tolerised (mesenteric LNs), primed (axillary LNs), primed treated with control IgG (axillary LNs) and primed treated with abatacept (axillary LNs). For CD11c+ cells cells were isolated by pooled secondary lymphoid organs (LNs and spleen).

2014-10-07 | E-GEOD-62089 | 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

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

RNA-seq of splenic and LN B cells from WT and Gm40600 Tg mice with or without LPS stimulation

Project description:We found that Gm40600 significantly affects plasmablast(PB)-like SP 2/0 cells. To explore the role of Gm40600 in B-cell especially plasma cell (PC) differentiation, we developed Gm40600 Transgenic (Gm40600 Tg) mice. B cells from spleen and lymph nodes (LNs) of WT and Gm40600 Tg mice were sorted by using B220 microbeads. B cells were also stimulated for 3 days by 10 ug/ml LPS. To explore the effect of Gm40600 overexpression on gene expression, we determined mRNA profiles in B cells from WT and Gm40600 Tg mice and LPS-stimulated B cells by RNA-seq. RNA-seq was done with an Illumina HiSeq 2500 instrument at GENEWIZ, Suzhou, China.

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Hydroxypropyl-Î²-cyclodextrin spikes local inflammation that induces Th2 and Tfh responses to the coadministered antigen

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2015-02-15 | E-GEOD-63332 | biostudies-arrayexpress

MPS vaccination alters long-term gene expression of antigen-presenting cells in lymph nodes

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2024-04-05 | E-MTAB-13698 | biostudies-arrayexpress

Inner ear supporting cells are organized tissue-resident macrophages arranged like cobblestones.

Project description:Sensorineural hearing loss (SHL) is a relatively common disease, and studies have suggested viral infection as a major cause. In the inner ear, the blood-labyrinthine barrier prevents access of the peripheral immune system; therefore, the immune system remains poorly understood. Here we found that cochlear accessory supporting cells (SCs), which are anchored by tight junctions, are organized tissue-resident macrophages. Virus-infected supporting cells change into activated macrophages and protect audiosensory receptor hair cells (HCs) against virus infection by producing interferon (IFN)-α/β. Moreover, we also observed bacterial phagocytosis by SCs. However, tumour necrosis factor-related apoptosis-inducing ligand (Trail), produced by virus-infected SCs, induced sensory hair loss and HC death by necroptosis. Notably, corticosteroid, the only effective drug for SHL, inhibited the virus-induced macrophage change of SCs. These results revealed an inner ear immune system, and suggest a possible mechanism for virus-induced SHL.

2016-12-10 | GSE89556 | GEO

Gene expression data of stromal cell subpopulations isolated from human lymph nodes (LNs) infiltrated with melanoma

Project description:Metastasis of human tumours to LNs is a universally negative prognostic factor. LN stromal cells (SCs) play a crucial role in enabling T cell responses, and since tumour metastases modulate their structure and function, this interaction may suppress immune responses to tumour antigens. However the SC subpopulations that respond to infiltration of malignant cells into human LNs have not been defined. Using microarray, we sought to assess gene expression profiles of two distinct SC subpopulations isolated from melanoma-infiltrated LNs. Our data demonstrate distinct profiles of two SC subpopulations isolated from melanoma-infiltrated LNs using fluorescence-activated cell sorting (FACS). FRCs express T cell modulating cytokines, chemokines and adhesion molecules, while CD34+ SCs predominantly express genes associated with ECM organization. Distinguishing between these two SC subpopulations in human LNs will now allow study of their respective impact on T cell responses to tumour antigens and clinical outcomes.

2020-06-26 | GSE150965 | GEO

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Project description:Regulatory T (Treg) are present in lymphoid and non-lymphoid tissues and restrict immune activation, prevent autoimmunity and regulate inflammation. While Treg in non-lymphoid tissues are typically resident, Treg in lymph nodes (LNs) predominantly recirculate and residency of Treg in LNs is poorly studied. Here, we show that 10-20% of all Treg in LNs are memory-like resident cells. Both thymic and peripheral Treg contributed to the pool of resident Treg and their residency did not require continuous TCR signaling. Yet, resident and circulating Treg had distinct TCR repertoires and different LNs contained distinct clonal subpopulations of resident Treg. We speculate that stochastic selection and variation in antigen availability governs commitment of individual T cell clones to the resident pool in each LN. Our results describe a framework for local fine-tuning of immune responses in LNs based on previous adaptive immune responses.

2022-02-04 | GSE195930 | GEO

RNA/WES/ATAC/scRNA sequencing of murine melanoma primary and LN metastases

Project description:The purpose of this study is to identify transcriptional, mutational, andepigenetic differences between LN metastases from primary tumors. Using in vivo serial passaging of the minimally metastatic syngeneic murine melanoma cell line B16-F0, we have generated nearly 300 unique cell lines spanning nine generations of in vivo passaging, derived from LNs, and exhibiting varying degrees of metastatic potential to LNs. Here, we perform mRNAseq on 30 of the lines representing a range of anatomical locations (distinct LNs), generations, and phylogenetic lineages. The subsequent differential expression analysis reveals a marked upregulation of immune-related genes. Additionally, we perform WES to identify differences in particular mutations, total mutational burden, and predicted neoantigen burden. Additionally, we perform ATAC-seq to assess changes in chromatin accessibility hat correlate with LN metastasis. We also perform scRNA-seq on dissociated LNs from mice with and without LN metastases.

2021-06-14 | GSE117529 | GEO

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