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Accession IconSRP066197

Transcriptional profiling of TH2 cells identifies pathogenic features associated with asthma

Organism Icon Homo sapiens
Sample Icon 160 Downloadable Samples
Technology Badge IconIllumina HiSeq 2500

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Allergic asthma and rhinitis are two common chronic allergic diseases that affect the lungs and nose, respectively. Both diseases share clinical and pathological features characteristic of excessive allergen-induced type 2 inflammation, orchestrated by memory CD4+ T cells that produce type 2 cytokines (TH2 cells). However, a large majority of subjects with allergic rhinitis do not develop asthma, suggesting divergence in disease mechanisms. Since TH2 cells play a pathogenic role in both these diseases and are also present in healthy non-allergic subjects, we performed global transcriptional profiling to determine whether there are qualitative differences in TH2 cells from subjects with allergic asthma, rhinitis and healthy controls. TH2 cells from asthmatic subjects expressed higher levels of several genes that promote their survival as well as alter their metabolic pathways to favor persistence at sites of allergic inflammation. In addition, genes that enhanced TH2 polarization and TH2 cytokine production were also upregulated in asthma. Several genes that oppose T cell activation were downregulated in asthma, suggesting enhanced activation potential of TH2 cells from asthmatic subjects. Many novel genes with poorly defined functions were also differentially expressed in asthma. Thus, our transcriptomic analysis of circulating TH2 cells has identified several molecules that are likely to confer pathogenic features to TH2 cells that are either unique or common to both asthma and rhinitis. Overall design: RNA-sequencing of circulating TH2 cells isolated from a cohort of patients with allergic rhinitis (25), asthma (40) patients and healthy non allergic subjects (15). Cells were directly isolated from blood by flow cytometry. Total RNA was extracted, messenger RNA was selected and cDNA was amplified linearly with a PCR based method (Picelli et al. 2014). Libraries were prepared using the NexteraXT Illumina sequencing platform.
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