Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD pathogenesis is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures, as well as macrophages, accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to increased lung compliance, total lung capacity, and mean linear chord length in WT, but not B cell-deficient mice, associated with an increased size and number of iBALT structures. The increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro co-culture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation. In summary, B cell function in iBALT formation in CS-induced emphysema provides a new innovative mechanism, which could be explored as a target for therapeutic intervention in COPD patients. Expression data of mice treated with cigarette smoke. Lung tissue was analysed at four and six months of age.

ORGANISM(S): Mus musculus

SUBMITTER: Johannes Beckers

PROVIDER: E-GEOD-52509 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD.

John-Schuster Gerrit G Hager Katrin K Conlon Thomas M TM Irmler Martin M Beckers Johannes J Eickelberg Oliver O Yildirim Ali Önder AÖ

American journal of physiology. Lung cellular and molecular physiology 20140815 9

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures and macrophages accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear. Here, w ...[more]

PMID: 25128521

Similar Datasets

Project description:Successful development of HIV-vaccination strategies will also depend on the ability to use novel approaches to analyse and integrate immunogenicity data generated in vaccine trials. The ANRS VAC 18 trial evaluated the immunogenicity of HIV-LIPO-5 vaccine (5 HIV peptides coupled to a palmytoil tail) administered at W0, 4, 12 and 24 in healthy volunteers. 62-69% of vaccinees developed HIV-specific ELISpot responses by W26. Here we present extensive immunogenicity assessments in a subset of vaccinees using ELISpot, lymphoproliferation, intracellular cytokine staining (ICS), cytokine multiplex and transcriptomic analyses. Peripheral blood mononuclear cells from volunteers collected before and following vaccinations were stimulated with HIV LIPO 5 vaccine, Gag peptides contained or not in the vaccine as controls. Different time points and stimulation conditions were compared, using false discovery rate to control for test multiplicity. 74% and 30% of vaccinees had cultured ELISpot and lymphoproliferation responses at W14, respectively. Ex-vivo ICS showed mainly single IL-2 producing cells. Secretion of IFN-Î³, TNF-Î±, IL-5, and IL-13 increased significantly in response to Gag stimulation after culture at W14 compared to W0. An induction of metallothionein genes was consistently detected after HIV-LIPO-5 stimulation at W0 and W14 related to the adjuvant effect of the lipid tail. After vaccination (W14), significant probes increased substantially (>1200 probes) including IFN-Î³, CXCL9, IL2RA, TNFAIP6, CCL3L1 and IL-6 W14 (fold change > 100%). In conclusion, HIV LIPO-5 vaccination elicited memory precursor responses with a Th1 and Th2 profile. The signature profile before vaccination provides information about the adjuvant effect of the lipid tail. Consistently with cytokine responses, vaccination is associated with a modulation in gene expression. This combined approach allowed to identify new signatures of HIV vaccine response and indicates that HIV-LIPO-5 could be further developed as a prime component of heterologous prime boost strategies. PBMC mRNA of 12 healthy volunteers, stimulate in four different conditions (HIV-LIPO-5, Gag+, Gag-, NS) during 6 and 24 hours before and after vaccination (week 0 and week 14)

Project description:Primary aldosteronism (PA) is the most common endocrine hypertension comprising 10% of hypertensive patients. A recent series of transcriptome analyses using DNA microarray has shown that neumerous genes are differentially expressed between aldosterone-producing adenoma (APA) and its adjacent adrenal gland (AAG) tissue from the same patient. However, the molecular mechanism(s) of pathogenesis of APA has not yet been fully clarified. Although growing body of evidence has shown that epigenetic abnormalities including DNA methylation play a key role in tumorigenesis, there are few studies with regard to DNA methylation in APA. In the present study, to elucidate the pathogenic relationship between gene expression and DNA methylation in PA, we conducted an integrated analysis of transcriptome and methylome data for paired APA-AAG samples from the same patient. Adrenal specimens were obtained from 7 Japanese patients with APA, who underwent adrenalectomy at Tokyo Medical and Dental University. RNA and DNA samples were extracted from those 7 paired APA and AAG tissues. Gene expression and genome-wide DNA methylation profiles were obtained using SurePrint G3 Human GE 8x60K Microarray (Agilent) and Infinium HumanMethylation450 Beadchip (Illumina), respectively. Transcriptome anlaysis identified 244 significantly (2 fold<) upregulated genes in APA compared to AAG. The upregulated genes include the previously studied genes such as PCP4, ALDH1A2, and CYP11B2, and other genes that have not been previously studied, such as HOXA9, HOXA11, and HOXB9. Gene ontology (GO) analysis for these upregulated genes identified the calcium signaling pathway to be most significantly enriched with the upregulated genes (8 genes). Methylome analysis revealed that APA was globally hypomethylated compared to AAG regardless of gene feature groups, namely, TSS1500, TSS200, 5’UTR, 1stExon, gene body, and 3’UTR. GO analysis for the genes showing hypomethylation at TSS1500/TSS200 regions in APA identified the term “cytokine-cytokine receptor interaction” to be most significantly enriched with hypomethylated genes (37 genes). Integrated analysis of gene expression and genome-wide DNA methylation profiles identified 18 genes that are upregulated and whose TSS1500/TSS200 regions are hypomethylated in APA compared to AAG. These genes include CYP11B2 and MC2R (ACTH receptor). In conclusion, this is the first genome-wide study for PA that integrated transcriptome and methylome data. Global DNA hypomethylation in APA and concordant transcriptional up-regulation of some key genes, such as CYP11B2 and MC2R, may play crucial roles in the pathophysiological significance in PA. Adrenal specimens were obtained from 7 Japanese patients with APA, who underwent adrenalectomy at Tokyo Medical and Dental University. RNA and DNA samples were extracted from those 7 paired APA and AAG tissues. Gene expression and genome-wide DNA methylation profiles were obtained using SurePrint G3 Human GE 8x60K Microarray (Agilent) and Infinium HumanMethylation450 Beadchip (Illumina), respectively.

Dataset Information

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

Publications

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets