Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Allergenic Can f 1 and its human homologue Lcn-1 direct dendritic cells to induce divergent immunity

ABSTRACT: Why and when the immune system skews to Th2 mediated allergic immune responses is still poorly characterized. With two homologous lipocalins, the major respiratory dog allergen Can f 1 and the human endogenous, non-allergenic Lipocalin-1, we investigated their impact on human monocyte derived dendritic cells (DC). The two lipocalins had differential effects on DC according to their allergenic potential. Compared to Lipocalin-1, Can f 1 persistently induced lower levels of the Th1 skewing maturation marker expression, tryptophan breakdown and IL-12 production in DC. As a consequence, T cells stimulated by DC treated with Can f 1 produced more of the Th2 signature cytokine IL-13 and lower levels of the Th1 signature cytokine IFN-γ than T cells stimulated by Lipocalin-1 treated DC. These data were partially verified by a second pair of homologous lipocalins, the cat allergen Fel d 4 and its putative human homologue MUP. Our data indicate that the crosstalk of DC with lipocalins alone has the potential to direct the type of immune response to these particular antigens. A global gene expression analysis further supported these results and indicated significant differences in intracellular trafficking, sorting and antigen presentation pathways when comparing Can f 1 and Lipocalin-1 stimulated DC. With this study we contribute to a better understanding of the induction phase of a Th2 immune response.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62436 | GEO | 2015/04/08

SECONDARY ACCESSION(S): PRJNA264093

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Microarray analyses of lymph node dendritic cells (DCs) stimulated in vitro with papain or LPS

2010-05-05 | GSE21602 | GEO

Microarray analysis of therapeutic (GM4) and non therapeutic (GM) NOD DC

Project description:We have previously demonstrated that bone marrow-derived DC can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes (T1D). The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules and secreted low levels of IL-12p70. The protective DC therapy induced regulatory Th2 cells that shifted the dominant Th1 environment, present in NOD mice, to a mixed Th1/Th2 milieu. Microarray analysis of therapeutic and non-therapeutic DC populations revealed several novel molecules that could play important roles in the observed DC-mediated therapy. The therapeutic DC population expressed a unique pattern of costimulatory molecules and chemokines, which were confirmed by flow cytometry and ELISA assays. We have performed in vitro chemotaxis assays that demonstrated the therapeutic DC preferentially attracted Th2 cells, as compared to Th1, Treg or naÃ¯ve T cells. In addition we quantified the in vivo migration of activated islet-specific T cells to the pancreas using novel cell labeling techniques and 19F nuclear magnetic resonance. A subcutaenous injection of therapeutic DC alters the migration of both Th1 and Th2 cells to the pancreas, and Th1 cells appeared in the lymph node draining the site of DC injection. These results suggest that the therapeutic function of DC is mediated in part by the chemoattractive properties of these DC for diabetogenic Th1 cells. Bone marrow cells from NOD mice were cultured in GM or GM + IL-4 to generate DC. DC were purified on metrizamide gradients after 4 days of culture. Purified DC were stimulated with LPS + IFNg and RNA taken 0, 6 and 20 hours after stimulation. Three biological replicates were performed but not all RNA samples were good. The are 3 replicates for GM/0, GM4/0, GM4/6 and 2 replicates for GM/6, GM/20 and GM4/20

2010-07-29 | E-GEOD-15320 | biostudies-arrayexpress

Microarray analysis of therapeutic (GM4) and non therapeutic (GM) NOD DC

Project description:We have previously demonstrated that bone marrow-derived DC can prevent diabetes development and halt progression of insulitis in NOD mice, the mouse model of type 1 diabetes (T1D). The DC population that was most effective in this therapy had a mature phenotype, expressed high levels of costimulatory molecules and secreted low levels of IL-12p70. The protective DC therapy induced regulatory Th2 cells that shifted the dominant Th1 environment, present in NOD mice, to a mixed Th1/Th2 milieu. Microarray analysis of therapeutic and non-therapeutic DC populations revealed several novel molecules that could play important roles in the observed DC-mediated therapy. The therapeutic DC population expressed a unique pattern of costimulatory molecules and chemokines, which were confirmed by flow cytometry and ELISA assays. We have performed in vitro chemotaxis assays that demonstrated the therapeutic DC preferentially attracted Th2 cells, as compared to Th1, Treg or naïve T cells. In addition we quantified the in vivo migration of activated islet-specific T cells to the pancreas using novel cell labeling techniques and 19F nuclear magnetic resonance. A subcutaenous injection of therapeutic DC alters the migration of both Th1 and Th2 cells to the pancreas, and Th1 cells appeared in the lymph node draining the site of DC injection. These results suggest that the therapeutic function of DC is mediated in part by the chemoattractive properties of these DC for diabetogenic Th1 cells.

2010-06-24 | GSE15320 | GEO

Microarray analyses of lymph node dendritic cells (DCs) stimulated in vitro with papain or LPS

Project description:T helper type 2 (Th2) responses are induced by protease allergens and helminthes. However the molecular mechanisms that initiate Th2 responses are poorly understood. To obtain insight into this mechanism, we performed a microarray analysis of lymph node DCs stimulated in vitro with the protease allergen papain, or with LPS, a Th1 inducing stimulus. Key words: Th2 response, LPS, dendritic cells, Papain CD11c+ DCs were isolated from the lymph nodes of C57BL/6 mice, and cultured in vitro (1x106 DCs per ml) with 500 3T3-CD40L fibroblasts, either alone, or in the presence of papain (25 µg/ml) or LPS (1 µg/ml). 4h and 17h later, the cells were harvested and RNA isolated and processed for microarray analyses. RNA was extracted and processed from freshly isolated LN DCs. For a given time point, the expression profile of DCs treated with papain or LPS, were compared to that of untreated DCs

2010-05-05 | E-GEOD-21602 | biostudies-arrayexpress

B bifidum actively changes the gene expression profile induced by L acidophilus in murine dendritic cells

Project description:Dendritic cells (DC) play a pivotal regulatory role in activation of the innate as well as the adaptive part of the immune system by responding to environmental microorganisms. We have previously shown that some lactobacilli strains induce a strong production of the pro-inflammatory and Th1 polarizing cytokine IL-12 in DC. Contrary, bifidobacteria do not induce IL-12, but are able to inhibit the IL-12 production induced by lactobacilli. In the present study, genome wide microarrays were used to investigate the maturation and gene expression pattern murine bone marrow derived DC stimulated with Lactobacillus acidophilus NCFM and Bifidobacterium bifidum Z9. L. acidophilus NCFM strongly induced expression of interferon (IFN)-Î², multiple virus defence genes, and cytokine and chemokine genes related to both the adaptive and the innate immune response. Contrary, B. bifidum Z9 mostly up-regulated genes encoding cytokines and chemokines related to the innate immune response. Moreover, B. bifidum Z9 inhibited the expression of the genes initiating the adaptive immune response induced by L. acidophilus NCFM and had an additive effect on genes of the innate immune response and some Th2 skewing genes. The gene encoding Jun dimerization protein 2 (JDP2), a key regulator in cell signalling, was one of the few genes only induced by B. bifidum Z9. Blocking of the JNK1/2 pathway completely inhibited the gene expression of Ifn-Î². We suggest that B. bifidum Z9 employs an active mechanism to inhibit induction of genes in DC triggering the adaptive immune system and that JPD2 is involved in the regulatory mechanism. In the experiment saline control, Lactobacillus acidophilus NCFM, Bifidobacterium bifidum Z9 or both bacteria were were added to murine dendritic cells and stimulated for 10 hours. Experiments were run in triplicates and analyzed in a Two-way ANOVA design.

2010-02-24 | E-GEOD-20302 | biostudies-arrayexpress

Proteomic analysis of T cell differentiation

Project description:T helper cells (Th) play an important role guarding, regulating and modulating immune responses. The different Th lineages fulfill different tasks in response to infections. The two best defined subtypes are Th1 (involved in cellular immunity) and Th2 (humoral immunity). The cytokine environment after activation determines the differentiation path of a Th cell. We defined a strategy to investigate the differentiation signature of T helper cells with a proteomics approach. Murine primary naïve CD4+ T-cells from spleen were differentiated and activated in vitro. After 3 days of differentiation proteins were analysed. The proteomic profile of the Th1 and Th2 cells will help understand these phenotypes better, which is important in finding therapeutic targets for disease and for the development of effective vaccines.

2019-02-14 | PXD004532 | Pride

In vivo LPS responses in murine splenic CD8 and CD11b DC subsets

Project description:Background: Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 bias, generating inducible Tregs, and inducing tolerance. Multiple DC subsets have been identified in the mouse that are thought to have evolved to control these different immune outcomes. However, how these subsets differentially respond to inflammatory and/or tolerogenic signals in order to accomplish their divergent functionality remains unclear. Results: We analysed the responses of murine, splenic CD8 and CD11b DC subsets to in-vivo stimulation with lipopolysaccharide using RNA-Seq and systems biology approaches and observed responses are highly subset-specific. We reanalysed multiple datasets from the literature and show that these subset responses are obscured when analysing signaling at the population level. We show that the subset-specificity is due to the unique regulation of distinct TLR4 pathway modulators that ‘fine-tune’ a common TLR4 cascade rather and not due to major differences in signaling pathways or transcription factors. Conclusions: We propose the Pathway Modulation Model wherein common signaling pathways are regulated by unique sets of modulators allowing for distinct immune responses in closely related DC subsets. We extend these observations using analagous datasets from the literature and show that our model provides a global mechanism for generating cell subset-specific signaling in multiple subpopulations in mouse and man. Splenic CD8 and CD11b DC subsets from LPS stimulated (10 pooled animals) and Control (5 pooled animals) mice were analysed by RNA-Seq.

2014-07-01 | E-GEOD-42573 | biostudies-arrayexpress

Fasciola hepatica Fatty Acid Binding Protein 1 modulates T cell polarization by promoting dendritic cell thrombospondin-1 secretion without affecting metabolic homeostasis in obese mice

Project description:The immunomodulatory effects of recombinant F. hepatica FABP1 (fhFABP1) on monocyte-derived human DCs (moDCs) and the underlying mechanism were investigated using various approaches, including DC-allogenic T cell co-culture and DC phenotyping through transcriptomic, proteomic and FACS analyses. We found that fhFABP1 induced a tolerogenic-like phenotype in LPS-stimulated moDCs characterized by a dose-dependent increase in the cell-surface tolerogenic marker CD103 and IL-10 secretion, while DC co-stimulatory markers were not affected. A significant decrease in secretion of the pro-inflammatory cytokines IL-12p70 and IL-6 was also observed. In addition, these effects were associated with an increase in both Th2-on-Th1 ratio and IL-10 secretion by CD4+ T cells following DC-T cell co-culture. RNA sequencing and targeted proteomic analyses identified thrombospondin-1 (TSP-1) as a non-canonical factor highly expressed and secreted by fhFABP1-primed moDCs. The effect of fhFABP1 on T cell skewing was abolished when using an TSP-1 blocking antibody during DC-T cell co-culture. Immunomodulation by helminth molecules has also been linked to improved metabolic homeostasis during obesity. In vivo, although fhFABP1 injection in high-fat diet-fed obese mice induced a potent Th2 immune response in adipose tissue, it did not improved insulin sensitivity or glucose homeostasis.

2022-06-22 | GSE197462 | GEO

Dendritic cell maturation by proinflammatory TNF or pathogenic Trypanosoma brucei antigens instruct similar T helper-2 cell responses in murine models of autoimmunity and asthma

Project description:Background Dendritic cells (DC) represent the major cell type leading to polarized T helper (Th) cell responses in vivo. The current data indicate that DC maturation under inflammatory conditions or by helminth infections induce only incomplete DC maturation bearing a partially tolerogenic potential. Such semi-mature DC promoted a Th2 profile with increasing proportions of regulatory IL-10 producing T cells (Tr-1) upon restimulation. Methodology/Principal Findings Here we asked whether the instruction of DC by the proinflammatory cytokine TNF is qualitatively different from maturation by two types of variant surface glycoproteins (VSGs) of Trypanosoma brucei. We tested differentially matured murine bone marrow (BM)-derived DC for changes in surface markers or cytokines, by microarray analyses, for their induction of Th2 responses and their capacity to influence the disease models asthma for Th2 immunity and experimental autoimmune encephalomyelitis (EAE) for a Th1/Th17 response. Conclusions/Significance Together, our data suggest that the partial maturation signatures induced by TNF and VSG antigens are highly similar and result in comparable Th2/Tr1 profiles, effects on asthma and EAE. This is remarkable since the responses resulting from endogenous inflammatory TNF-receptor signals or exogenous pathogenic MyD88 ligands are comparable. total samples analysed are 5

2012-03-19 | E-GEOD-28231 | biostudies-arrayexpress

Profiling of Jurkat T cells activated with CD3, CD28 and PMA at 1 and 8 hours

Project description:T lymphocytes are orchestrators of adaptive immunity. Naïve T cells may differentiate into the Th1, Th2, Th17 or iTreg phenotype, depending on environmental co-stimulatory signals. In order to identify the genes and pathways involved in differentiation of Jurkat T cells towards Th1 and Th2 subtypes we performed comprehensive transcriptome analyses of Jurkat T cells stimulated with various stimuli an pathway inhibitors

2011-07-16 | GSE30676 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data