A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis

Benson, Mikael; Carlsson, Lena; Guillot, Gilles; Jernås, Margareta; Langston, Michael A.; Rudemo, Mats; Åndersson, Bengt

doi:10.1038/sj.gene.6364322

Cited by 29 publications

(32 citation statements)

References 33 publications

(57 reference statements)

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“…Several of these genes and pathways have a previously described role in AA pathogenesis, validating that our experimental approach is sufficiently sensitive to capture disease-relevant processes. 10,33 Although it has been shown that NK cells aggregate perifollicularly in AA lesional skin 3,4,34 and peripheral blood, 35,36 there is limited data regarding the role of NK cells in AA pathogenesis. Our data show an upregulation of NK-cell cytotoxicity in AA peripheral blood that, as suggested by others, 11,12,37 may promote the failure of hair follicle immune privilege.…”

Section: Resultsmentioning

confidence: 99%

Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity

Coda¹,

Hysa²,

Seiffert-Sinha³

et al. 2010

Genes Immun

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Alopecia areata (AA) is an autoimmune hair loss disorder in which systemic disturbances have been described, but are poorly understood. To evaluate disease mechanisms, we examined gene expression in the blood of defined clinical subgroups (patchy AA persistent type, AAP, n ¼ 5; alopecia universalis, AU, n ¼ 4) and healthy controls (unaffected relatives, UaR, n ¼ 5; unaffected non-relatives, UaNR, n ¼ 4) using microarrays. Unsupervised hierarchical clustering separates all four patient and control groups, producing three distinct expression patterns reflective of 'inheritance', 'disease' and 'severity' signatures. Functional classification of differentially expressed genes (DEGs) comparing disease (AAP, AU) vs normal (UaR) groups reveals upregulation in immune response, cytokine signaling, signal transduction, cell cycle, proteolysis and cell adhesionrelated genes. Pathway analysis further reveals the activation of several genes related to natural killer-cell cytotoxicity, apoptosis, mitogen activated protein kinase, Wnt signaling and B-and T-cell receptor signaling in AA patients. Finally, 35 genes differentially expressed in AA blood overlap with DEGs previously identified in AA skin lesions. Our results implicate innate and adaptive immune processes while also revealing novel pathways, such as Wnt signaling and apoptosis, relevant to AA pathogenesis. Our data suggest that peripheral blood expression profiles of AA patients likely carry new biomarkers associated with disease susceptibility and expression.

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Section: Resultsmentioning

confidence: 99%

Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity

Coda¹,

Hysa²,

Seiffert-Sinha³

et al. 2010

Genes Immun

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“…Unlike in most complex diseases, in SAR it is possible to mimic the disease process by obtaining CD4+ T cells outside of the pollen season, when the patients are asymptomatic, and challenge in vitro with pollen or diluent. Thus, it is possible to identify disease-specific changes by comparing expression differences from allergen-and diluent-challenged cells from patients with those observed in controls (Benson et al 2006a;Bosco et al 2009). This comparison will henceforth be referred to as a delta-delta (ΔΔ) expression analysis.…”

Section: Results Mirnas Regulate Disease-relevant Mrna Modules In Hummentioning

confidence: 99%

“…Paired samples were generated by culturing the CD4+ T cells with allergen or diluent according to the method previously described (Benson et al 2006a). We performed miRNA-and mRNAexpression profiling using Illumina's Human v2 miRNA panel and HumanWG-6 v3.0 Expression BeadChips (Illumina), respectively, on the allergen-and diluent-challenged samples derived from all the 40 subjects, according to the manufacturer's instructions.…”

Section: Mirna-and Gene-expression Profilingmentioning

confidence: 99%

MicroRNAs act complementarily to regulate disease-related mRNA modules in human diseases

Chavali

Bruhn

Tiemann

et al. 2013

RNA

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MicroRNAs (miRNAs) play a key role in regulating mRNA expression, and individual miRNAs have been proposed as diagnostic and therapeutic candidates. The identification of such candidates is complicated by the involvement of multiple miRNAs and mRNAs as well as unknown disease topology of the miRNAs. Here, we investigated if disease-associated miRNAs regulate modules of disease-associated mRNAs, if those miRNAs act complementarily or synergistically, and if single or combinations of miRNAs can be targeted to alter module functions. We first analyzed publicly available miRNA and mRNA expression data for five different diseases. Integrated target prediction and network-based analysis showed that the miRNAs regulated modules of disease-relevant genes. Most of the miRNAs acted complementarily to regulate multiple mRNAs. To functionally test these findings, we repeated the analysis using our own miRNA and mRNA expression data from CD4+ T cells from patients with seasonal allergic rhinitis. This is a good model of complex diseases because of its well-defined phenotype and pathogenesis. Combined computational and functional studies confirmed that miRNAs mainly acted complementarily and that a combination of two complementary miRNAs, miR-223 and miR-139-3p, could be targeted to alter disease-relevant module functions, namely, the release of type 2 helper T-cell (Th2) cytokines. Taken together, our findings indicate that miRNAs act complementarily to regulate modules of disease-related mRNAs and can be targeted to alter disease-relevant functions.

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“…Interestingly, in our study we found the TNFRSF17 gene of the same superfamily to be up-regulated most strongly of all immunologic genes (Table 1). Although both studies differ: (a) one is a study into respiratory allergy, the other study is that of a food allergic model; (b) different species were studied; and, (c) Benson et al (2006) studied allergen-specific T-lymphocytes, whereas we studied a pool of MLN cells. With both studies in mind, one could further substantiate the claim that the proliferation of allergen-challenged T H 2 cells is associated with an increase in TNFRSF-family signaling.…”

Section: Discussion and Conlusionsmentioning

confidence: 99%

“…However, microarray data of respiratory allergy studies are available. Benson et al (2006) performed a network-based analysis of DNA microarray data from allergen-challenged CD4 + T-lymphocytes from patients with seasonal allergic rhinitis. They found a strong upregulation of expression of TNFRSF4, one of the genes of the TNF superfamily, which is involved in regulation of apoptosis and T H 2 proliferation.…”

Section: Discussion and Conlusionsmentioning

confidence: 99%

Gene expression changes in the mesenteric lymph nodes of rats after oral peanut extract exposure

Jonge

Pennings

Baken

et al. 2008

Journal of Immunotoxicology

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A network-based analysis of allergen-challenged CD4+ T cells from patients with allergic rhinitis

Cited by 29 publications

References 33 publications

Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity

Peripheral blood gene expression in alopecia areata reveals molecular pathways distinguishing heritability, disease and severity

MicroRNAs act complementarily to regulate disease-related mRNA modules in human diseases

Gene expression changes in the mesenteric lymph nodes of rats after oral peanut extract exposure

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