Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

45 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lung conventional dendritic cells promote mucosal adjuvant activity of flagellin

ABSTRACT: The activity of the potent nasal adjuvant flagellin depends on initial activation of airway epithelilal cells. This study aims at investigating the immune cells involved in the antigen presentation within the respiratory tract. First, microarrays characterized that activation/recruitment of immune cells was the main signature of flagellin activation in lung. Neutrophils and classical monocytes were strongly recruited into the lungs and take up antigen upon nasal administration of flagellin. In contrast, the numbers of lung CD11b+ or CD103+ DC and alveolar macrophages were not enhanced although these cells were very efficient in antigen uptake. Our experiments showed that CD11b+ DC but not monocytes, PMN, CD103+ DC are not essential for the adjuvant effect. Flagellin signaling enhanced the functional activation of lung CD11b+ conventional DC and their migration to the lymph nodes. Using Cd11c-DTR mice, CD11b+ DC from lymph nodes were identified as the major stimulators of CD4 T cell activation. Finally, the migration and maturation of mucosal DC was independent of direct signaling, highlighting the contribution of epithelial factors in the mucosal adjuvant effect of flagellin. In conclusion, these data demonstrate that adjuvant activity can be dissociated from inflammatory cell recruitment an open new perpectives for improvement of vaccines. Female C57BL/6J (6 weeks old) mice were immunized with the TLR5 agonist Flagellin (1Î¼g diluted in PBS) by intranasal (i.n.) administration. Blood samples of four time points post immunization were taken at 2h, 4h, 18h and 48h. Microarray experiments were performed as single-color hybridizations.

ORGANISM(S): Mus musculus

SUBMITTER: Hans-Joachim Mollenkopf

PROVIDER: E-GEOD-46421 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Lung conventional dendritic cells promote mucosal adjuvant activity of flagellin

Project description:The activity of the potent nasal adjuvant flagellin depends on initial activation of airway epithelilal cells. This study aims at investigating the immune cells involved in the antigen presentation within the respiratory tract. First, microarrays characterized that activation/recruitment of immune cells was the main signature of flagellin activation in lung. Neutrophils and classical monocytes were strongly recruited into the lungs and take up antigen upon nasal administration of flagellin. In contrast, the numbers of lung CD11b+ or CD103+ DC and alveolar macrophages were not enhanced although these cells were very efficient in antigen uptake. Our experiments showed that CD11b+ DC but not monocytes, PMN, CD103+ DC are not essential for the adjuvant effect. Flagellin signaling enhanced the functional activation of lung CD11b+ conventional DC and their migration to the lymph nodes. Using Cd11c-DTR mice, CD11b+ DC from lymph nodes were identified as the major stimulators of CD4 T cell activation. Finally, the migration and maturation of mucosal DC was independent of direct signaling, highlighting the contribution of epithelial factors in the mucosal adjuvant effect of flagellin. In conclusion, these data demonstrate that adjuvant activity can be dissociated from inflammatory cell recruitment an open new perpectives for improvement of vaccines.

2014-01-01 | GSE46421 | GEO

Mouse lung CD103+ and CD11b-high dendritic cell (DC) subsets

Project description:Mouse lung CD11c+ dendritic cells are composed of 2 major DC subsets, the CD103+CD11b-low/intermediate DC (CD103+ DC) and the CD11b-highCD103- DC (CD11b-high DC). These 2 subsets are functionally distinct. Comparison of their functions showed CD103+ DC Microarray analysis was performed to compare the gene expression profiles of the 2 lung DC subsets in naÃ¯ve mice. Perfused lungs from 6-8-week naÃ¯ve BALB/cByJ mice were pooled and digested with collagenase D. CD11c+ cells were selected by anti-CD11c magnetic microbeads (Miltenyi) and stained by fluorochrome-conjugated mAb against I-A, CD103, CD11b, and CD11c plus 7-

2010-03-24 | E-GEOD-17322 | biostudies-arrayexpress

Mouse lung CD103+ and CD11b-high dendritic cell (DC) subsets

2010-03-15 | GSE17322 | GEO

Transcriptional profiling of small intestinal lamina propria Dendritic cells by microarray

Project description:CD103+CD11b+ dendritic cells (DC) are unique to the intestine, but the factors governing their differentiation are unclear. Here we show that transforming growth factor receptor 1 (TGF beta 1) has an indispensable, cell intrinsic role in the development of these cells. Deletion of Tgfbr1 results in markedly fewer intestinal CD103+CD11b+ DCs and a reciprocal increase in the CD103–CD11b+ DC subset. Transcriptional profiling identifies markers that define the CD103+CD11b+ DC lineage, including CD101, TREM1 and Siglec-F, and shows that the absence of CD103+CD11b+ DCs in CD11c-Cre.Tgfbr1fl/fl mice reflects defective differentiation from CD103–CD11b+ intermediaries, rather than an isolated loss of CD103 expression. The defect in CD103+CD11b+ DCs is accompanied by reduced generation of antigen-specific, inducible FoxP3+ regulatory T (Treg) cells in vitro and in vivo, and by reduced numbers of endogenous TH17 cells in the intestinal mucosa. Thus, TGF beta 1 mediated signalling may explain the tissue-specific development of these unique DCs.

2017-06-23 | GSE100393 | GEO

Mouse lung transcriptional response to flagellin stimulation

Project description:Vaccine adjuvants enhance adaptive immunity to co-administered antigens. Whereas the modes of action are multiple, the activation of antigen-presenting cells (APC) like dendritic cells by adjuvants is a prerequisite. Detection of microbial signals by innate sensors like Toll-like receptors (TLR) is a major mechanism of APC activation. Most candidate or licensed vaccines assume that adjuvant activity of TLR agonists depends on direct effect on APCs. This study addressed whether TLR stimulation of non-hematopoietic cells could contribute to the adjuvant effect. Nasal administration of flagellin enhanced T cell- and antibody-mediated immunity to co-administered antigens in a TLR5-dependent but inflammasome-independent manner. We found that lung radioresistant cells were sufficient to promote immunity, thereby suggesting that direct TLR5-mediated APC stimulation is dispensable to adjuvant activity. Consistent with this, radioresistant compartment is essential to stimulate the swift TLR5-dependent transcription. The transcriptional response was restricted to the epithelial compartment and was associated to the production of a narrow set of mediators including the chemokine CCL20, known to promote APC recruitment in mucosal tissues. Besides, flagellin was rapidly degraded in lower airways and was not transported into lung parenchyma or peripheral tissues. This study therefore suggests an unexpected mechanism for how TLR agonists act as adjuvant and how epithelium is instrumental to sense and integrate microbial signals to promote adaptive immunity. In conclusion, the immune-enhancing effect of adjuvants on epithelial cells can be harnessed for improving vaccines. 1 µg of flagellin was instillated intranasally to LPS-unresponsive C3H/HeJ mice. Total lung RNA was extracted 1h later and prepare for hybridization on Affymetrix microarrays.

2013-03-22 | E-GEOD-45369 | biostudies-arrayexpress

RNA-seq of lung myeloid cells from WT and Ptgs2-cKO mice

Project description:To investigate the role of the COX-2-dependent lung fibroblast program in reprogramming lung myeloid cells, we generated fibroblast-targeted Ptgs2 conditional knockout mice by crossing Pdgfra-Cre mice with Ptgs2flox/flox mice. Then we isolated two primary types of lung resident DCs-CD103+ conventional DC (cDC1) and CD11b+ conventional DC (cDC2), and lung monocytes from WT and Ptgs2 cKO mice by fluorescence-activated cell sorting and performed RNA sequencing.

2022-07-19 | E-MTAB-11888 | biostudies-arrayexpress

Retinoic acid directs the development and transcriptional programming of intestinal dendritic cells

Project description:This file contains gene microarray data from bone marrow pre-ul DC, in vitro derived CD103+CD11b+ and CD103+CD11b- cDC with or without retinoic acid.

2015-08-01 | GSE68399 | GEO

Retinoic acid directs the development and transcriptional programming of intestinal dendritic cells

Project description:This file contains gene microarray data from bone marrow pre-ul DC, in vitro derived CD103+CD11b+ and CD103+CD11b- cDC with or without retinoic acid. We analyze transcript expression data from bone marrow pre-uDC, Splenic and SI cDC1 and cDC2 (GSE15907 - 18 samples), in vitro derived CD103+CD11b+ and CD103+CD11b- cDC from C57Bl/6 mice. The complete dataset is linked below as a supplementary file.

2015-08-01 | E-GEOD-68399 | biostudies-arrayexpress

Transcriptome profiles of mouse and human monocyte and dendritic cell subsets (human data)

Project description:Dendritic cells (DCs) are critical in mediating immunity to pathogens, vaccines, tumors and tolerance to self. Significant progress has been made in the study of DC subsets in murine models but the translation of these findings to human DC immunobiology has not been fully realized. Murine splenic CD8+ DC and CD103+ DC possess potent antigen cross-presenting capacity. Although recent evidence points to human blood CD141+ DCs as the functional equivalent of CD8+ DC, the precise identity of the human migratory cross-presenting DC has remained elusive. We performed phenotypic and functional analyses to interrogate the DC compartment of human non-lymphoid tissues and identified three distinct subsets: i) CD141high DCs, ii) CD1c DCs and iii) CD14+ DCs. Only CD141high DCs were capable of cross-presenting soluble antigen. Comparative transcriptome analysis of steady state monocyte and DC subsets between mouse and human confirmed conservation between species, aligning the following subsets together: i) human CD141high DCs with mouse CD8+ and CD103+ DCs, ii) human CD1c+ DCs with mouse CD4+ DCs and iii) human CD14+ DC with mouse monocyte subsets. The lack of positive association between human CD1c+ DCs and mouse non-lymphoid tissue CD11b+ DCs highlights heterogeneity and predicts the existence of a monocyte-like cell within the CD11b+ DCs. Gene expression analysis using total RNA from specific human and mouse monocyte and dendritic cell subsets purified by FACS.

2012-07-11 | E-GEOD-35457 | biostudies-arrayexpress

Transcriptome profiles of mouse and human monocyte and dendritic cell subsets (mouse data)

2012-07-11 | E-GEOD-35458 | biostudies-arrayexpress