DNA Arrays in Allergy and Immunology

Schmidt‐Weber, Carsten B.; Wohlfahrt, Jan G.; Blaser, Kurt

doi:10.1159/000049489

Cited by 19 publications

(16 citation statements)

References 36 publications

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“…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%

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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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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“…CCL22 has been shown to play an important role in various diseases and mouse disease models. For example, elevated levels of CCL22 have been found in affected tissue of patients suffering from atopic dermatitis (10), atopic asthma (10), and contact hypersensitivity (11). Furthermore, CCL22 has been shown to be critically involved in mouse models of allergen-induced lung inflammation (12), atopic dermatitis (13), and septic peritonitis (14).…”

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confidence: 99%

Differential Regulation of CCL22 Gene Expression in Murine Dendritic Cells and B Cells

Ghadially

Ross

Kerst

et al. 2005

The Journal of Immunology

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The activated T cell-attracting CC chemokine CCL22 is expressed by stimulated B cells and mature dendritic cells (DC). We have cloned and sequenced the complete mouse gene, including 4 kb of the 5′-flanking promoter region, and detected two distinct sites for initiation of transcription by 5′-RACE. Reporter gene assays indicate that the promoter reflects the specificity of the endogenous gene. Within the proximal promoter region, we identified potential binding sites for NF-κB, Ikaros, and a putative GC box. All three regions bind proteins. The NF-κB site was shown to specifically bind NF-κB subunits p50 and p65 from nuclear extracts of LPS-stimulated B cells, B cell line A20/2J, TNF-α-stimulated bone marrow-derived DC, and DC line XS106. Furthermore, promoter activity was affected by targeted mutagenesis of the NF-κB site and transactivation with p50 and p65. The region harboring the putative Ikaros site contributes to promoter activity, but the binding protein does not belong to the Ikaros family. The GC box was shown to specifically bind Sp1 using extracts from LPS-stimulated B cells and A20/2J but not from DC and DC line XS106. Additionally, Sp1 transactivated the promoter in A20/2J but not in XS106 cells, and mutation of the Sp1 site diminished transactivation. Furthermore, binding of the protein complex at the GC box is required for NF-κB activity, and the spatial alignment of the binding sites is of critical importance for promoter activity. Thus, identical and distinct proteins contribute to expression of CCL22 in DC and B cells.

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“…In addition, no appropriate cell lines are available for further in vitro functional studies, other than leukemic cell lines such as Eol1 (Saito et al 1985) and AML14.3D10 (Baumann and Paul 1998). Recent developments in the technology of gene expression analysis, such as differential display (DD) (Liang and Pardee 1992;Ito et al 1994), DNA microarray (Schmidt-Weber et al 2001;Granucci et al 2001), and real-time RT-PCR (Lie and Petropoulos 1998;Kafert et al 1999) make it possible to efficiently survey the expression of large numbers of genes in small amounts of clinical samples, and new data on eosinophil accumulation and actions in pathological conditions are being accumulated.…”

Section: Comprehensive Gene Expression Analysis In Eosinophils From Pmentioning

confidence: 99%

The NR4A nuclear receptor family in eosinophils

Hashida¹,

Ohkura²,

Saito

et al. 2006

J Hum Genet

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It is well-known that many members of the family of nuclear receptors have been implicated in human diseases, and metabolic disorders in particular. The NR4A nuclear receptor family consists of three members, Nur77, Nurr1, and NOR1. All of these are orphan receptors, and Nur77 and NOR1 exert possible pathological roles in immune diseases through the modulation of leukocyte functions. CD30 stimulation, which induces eosinophil-specific apoptosis, markedly enhances expression of Nur77 and NOR1 in eosinophils. This suggests the possibility of pharmacological modulation of Nur77-or NOR1-specific apoptotic pathways via receptor-dependent transactivation. In this review, we discuss treatment of allergic diseases by low molecular weight compounds acting through the NR4A receptor family to cause eosinophil apoptosis. NR4A nuclear receptor genes were selected following comprehensive analysis of differentially expressed genes in eosinophils of atopic dermatitis patients compared with healthy volunteers.

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DNA Arrays in Allergy and Immunology

Cited by 19 publications

References 36 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

Differential Regulation of CCL22 Gene Expression in Murine Dendritic Cells and B Cells

The NR4A nuclear receptor family in eosinophils

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