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CDC42-related genes are upregulated in helper T cells from obese asthmatic children

Deepa Rastogi1, John Nico1, Andrew D Johnston2

  • 1Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY.

The Journal of Allergy and Clinical Immunology
|May 9, 2017
PubMed

Insights

Pediatric obesity worsens asthma severity. The CDC42 pathway is upregulated in T cells of obese children with asthma, contributing to inflammation and reduced lung function.

Area of Science:

  • Immunology
  • Pediatric Pulmonology
  • Genetics

Background:

  • Pediatric obesity-related asthma is more severe and less responsive to standard treatments compared to asthma in normal-weight children.
  • Obese asthmatic children exhibit nonatopic TH1-polarized systemic inflammation, which correlates with impaired pulmonary function, but the underlying mechanisms remain unclear.

Purpose of the Study:

  • To compare the CD4+ T-cell transcriptome between obese and normal-weight children with asthma.
  • To identify key differentially expressed genes associated with TH1-polarized inflammation in pediatric asthma.

Main Methods:

  • Directional RNA sequencing was employed to compare CD4+ T-cell transcriptomes in 21 obese and 21 normal-weight children with asthma.
  • Differential gene expression findings were verified in an initial cohort and validated in a second cohort using quantitative RT-PCR.

Main Results:

  • Differential gene expression analysis revealed enrichment of genes related to CDC42, a small guanosine triphosphate protein involved in T-cell activation, in obese asthmatic children.
  • Upregulation of MLK3 and PLD1, downstream of CDC42, and inverse correlations of CDC42EP4 and DOCK5 with FEV1/FVC ratio suggest CDC42's role in TH1 polarization and pulmonary deficits.

Conclusions:

  • The CDC42 pathway is identified as a novel target, upregulated in TH cells of obese children with asthma.
  • This pathway is implicated in the nonatopic TH1-polarized systemic inflammation and pulmonary function deficits observed in pediatric obesity-related asthma.
Abstract

Keywords:
Asthmachildrenhelper T cell transcriptomeobesity

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