T Cell Phenotype in Allergic Asthma and Atopic Dermatitis

Wohlfahrt, Jan G.; Kunzmann, Steffen; Menz, G; Kneist, W.; Akdiş, Cezmi A.; Blaser, Kurt; Schmidt‐Weber, Carsten B.

doi:10.1159/000072139

Cited by 31 publications

(31 citation statements)

References 42 publications

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“…Identification of novel Th2-associated clusters in HDM-stimulated PBMC. PBMC from 20 atopics and 20 nonatopics were cultured in the presence or absence of HDM for the indicated time points (12,24, or 48 h). Total RNA was extracted and pooled into six separate groups: AT1 (pool of 5 atopics), AT2 (pool of 5 atopics), AT3 (pool of 10 atopics), NA1 (pool of 5 nonatopics), NA2 (pool of 5 nonatopics), NA3 (pool of 10 nonatopics).…”

Section: Study Design and Statistical Analysesmentioning

confidence: 99%

“…Collectively, these studies indicate that individual immune responses typically involve up-regulation of multiple hundreds of genes (7)(8)(9). This technology has also been applied in the allergy field to study Th2 responses and related signaling pathways in freshly isolated T cells (10), polyclonally stimulated T cells (11,12), allergen-specific T cell clones and lines (13,14), polarized Th1/Th2 cell lines (15)(16)(17)(18)(19)(20), and in animal models (21). A consistent finding in the studies was the substantial number of differentially expressed genes identified, however, the lack of consistency in the gene lists reported by each study is striking.…”

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confidence: 99%

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Identification of Novel Th2-Associated Genes in T Memory Responses to Allergens

Bosco

McKenna

Devitt

et al. 2006

The Journal of Immunology

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Atopic diseases are associated with hyperexpression of Th2 cytokines by allergen-specific T memory cells. However, clinical trials with recently developed Th2 inhibitors in atopics have proven disappointing, suggesting underlying complexities in atopy pathogenesis which are not satisfactorily explained via the classical Th1/Th2 paradigm. One likely possibility is that additional Th2-associated genes which are central to disease pathogenesis remain unidentified. The aim of the present study was to identify such novel Th2-associated genes in recall responses to the inhalant allergen house dust mite. In contrast to earlier human microarray studies in atopy which focused on mitogen-activated T cell lines and clones, we concentrated on PBMC-derived primary T cells stimulated under more physiological conditions of low dose allergen exposure. We screened initially for allergen-induced gene activation by microarray, and validated novel genes in independent panels of subjects by quantitative RT-PCR. Kinetic analysis of allergen responses in PBMC revealed an early wave of novel atopy-associated genes involved in signaling which were coexpressed with IL-4 and IL-4R, followed by a later wave of genes encoding the classical Th2 effector cytokines. We further demonstrate that these novel activation-associated Th2 genes up-regulate in response to another atopy-associated physiological stimulus bacterial superantigen, but remain quiescent in nonphysiological responses in primary T cells or cell lines driven by potent mitogens, which may account for their failure to be detected in earlier microarray studies.

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Section: Study Design and Statistical Analysesmentioning

confidence: 99%

mentioning

confidence: 99%

Identification of Novel Th2-Associated Genes in T Memory Responses to Allergens

Bosco

McKenna

Devitt

et al. 2006

The Journal of Immunology

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“…Wohlfahrt and colleagues (18), in another study of peripheral CD4 ϩ lymphocytes, comparing subjects with asthma with normal control subjects using cDNA microarray techniques, also found up-regulation of TGF-␤1 and other members of the TGF-␤ family. Furthermore, they found evidence for up-regulation of several other gene families in asthma, including those for chemokines, chemokine receptors, fibroblast growth factors, and matrix metalloproteinases and their inhibitors.…”

Section: Peripheral Blood Lymphocytesmentioning

confidence: 93%

“…15S-HETE may be involved in airway remodeling (16), whereas lipoxins are increasingly appreciated for their antiinflammatory properties (17). Likewise, detection of CX3CR1 is a novel finding, but was found previously to be elevated in peripheral CD4 ϩ lymphocytes of subjects with asthma compared with normal control subjects (18). Genes included in the serine proteinase inhibitor (serpin) family of protease inhibitors, such as cathepsin C and cathepsin G, were also identified as differentially regulated in subjects with asthma compared with control subjects, and their potential role in asthma has been supported by other expression profiling studies (19,20).…”

Section: Bronchial Biopsymentioning

confidence: 98%

Gene Expression Profiling in Human Asthma

Hansel

Diette²

2007

Proceedings of the American Thoracic Society

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Asthma is a chronic inflammatory disease of the lungs, characterized by airway hyperreactivity, mucus hypersecretion, and airflow obstruction. Despite recent advances, the genetic regulation of asthma pathogenesis is still largely unknown. Gene expression profiling techniques are well suited to study complex diseases and hold substantial promise for identifying novel genes and pathways in asthma; however, relatively few studies have been completed in human asthma. The few studies that have been done have identified many novel candidate genes and pathways in asthma pathogenesis, including ALOX15 and serine proteinase inhibitors cathepsin C and G. The interpretation of results of these studies should be cautious, as limitations include small sample sizes and heterogeneity of study populations and tissues sampled. In the future, the promise of gene expression studies would be enhanced by the use of larger sample sizes and attempts to standardize phenotype, sample collection techniques, and analysis. As the field of expression profiling in asthma advances, we hope it will improve our understanding of critical questions about mechanisms involved in susceptibility to the disease, as well as help to personalize care by improving appropriate selection of patients for prevention and treatment strategies.

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“…For this technique, RNA from diseasespecific tissue is required. Previous studies have shown that peripheral blood mononuclear cells (PBMCs) reflect diseasespecific changes in an organ, and can be used as a model for the characterisation and monitoring of asthma using microarrays [18][19][20]. Unstimulated PBMCs most closely resembles the in vivo activation state of these cells [21].…”

mentioning

confidence: 99%

Gene expression in CD4+ T-cells reflects heterogeneity in infant wheezing phenotypes

Kapitein

Mo²,

Nijhuis³

et al. 2008

European Respiratory Journal

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Although a marked increase in the reporting of wheezing symptoms since the mid1970s has been described, the underlying immunopathology of the different wheezing phenotypes has not been clarified. Since differences in gene expression might be involved, the objective of the present study was to identify gene expression profiles in CD4+ T-cells from two distinct infant wheezing phenotypes.The gene expression profiles of peripheral CD4+ T-cells were compared by means of microarray analysis of six transient wheezers, six persistent wheezers and seven healthy controls. The differentially expressed genes were subsequently validated by RT-PCR.The differential gene expression profiles reflected common immunological pathways involved in apoptosis or proliferation of T-cells. Furthermore, both wheezing phenotypes showed decreased expression of the complement component 5 receptor 1 gene, a gene involved in the regulation of bronchial responsiveness. Moreover, differences in gene expression profiles were found in genes involved in the immune response against respiratory syncytial virus, such as those encoding signal transducer and activator of transcription 1 and an inflammatory mediator showing enhanced production in asthma (prostaglandin E 2 receptor 2).The present findings suggest that clinical symptoms of wheeze are reflected in common immunological pathways, whereas differences between wheezing phenotypes are, in part, reflected in distinct gene expression profiles.

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T Cell Phenotype in Allergic Asthma and Atopic Dermatitis

Cited by 31 publications

References 42 publications

Identification of Novel Th2-Associated Genes in T Memory Responses to Allergens

Identification of Novel Th2-Associated Genes in T Memory Responses to Allergens

Gene Expression Profiling in Human Asthma

Gene expression in CD4+ T-cells reflects heterogeneity in infant wheezing phenotypes

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