CDC42-related genes are upregulated in helper T cells from obese asthmatic children
Authors: Toni Adrianne M Tobias
Fernando Macian
John Nico
Andrew D Johnston
Yurydia Jorge
Deepa Rastogi
John M Greally
Journal: Journal of Allergy and Clinical Immunology (2018)
Discipline: IMMUNOLOGY
Keywords: Asthma; children; helper T cell transcriptome; obesity.
Affiliations: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY. Electronic address: ., Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY., Department of Genetics, Albert Einstein College of Medicine, Bronx, NY., Department of Pathology, Albert Einstein College of Medicine, Bronx, NY.

Abstract:  Background: Pediatric obesity-related asthma is more severe and less responsive to medications than asthma in normal-weight children. Obese asthmatic children have nonatopic TH1-polarized systemic inflammation that correlates with pulmonary function deficits, but the pathways underlying TH1-polarized inflammation are not well understood. Objective: We compared the CD4+ T-cell transcriptome in obese children with asthma with that in normal-weight children with asthma to identify key differentially expressed genes associated with TH1-polarized inflammation. Methods: CD4+ T-cell transcriptome-wide differential gene expression was compared between 21 obese and 21 normal-weight children by using directional RNA sequencing. High-confidence differentially expressed genes were verified in the first cohort and validated in a second cohort of 20 children (10 obese and 10 normal-weight children) by using quantitative RT-PCR. Results: Transcriptome-wide differential gene expression among obese asthmatic children was enriched for genes, including VAV2, DOCK5, PAK3, PLD1, CDC42EP4, and CDC42PBB, which are associated with CDC42, a small guanosine triphosphate protein linked to T-cell activation. Upregulation of MLK3 and PLD1, genes downstream of CDC42 in the mitogen-activated protein kinase and mammalian target of rapamycin pathways and the inverse correlation of CDC42EP4 and DOCK5 transcript counts with FEV1/FVC ratio together support a role of CDC42 in the TH1 polarization and pulmonary function deficits found in patients with obesity-related asthma. Conclusions: Our study identifies the CDC42 pathway as a novel target that is upregulated in TH cells of obese asthmatic children, suggesting its role in nonatopic TH1-polarized systemic inflammation and pulmonary function deficits found in patients with pediatric obesity-related asthma. 

Retracted: No

PubPeer comments:
 The erratum does not include the duplication of actin bands ![file] , 
 We had probed the same blot sequentially for CDC42EP4, p38 and S6k1 since we wanted to quantify the three proteins in the same clinical samples. The same actin band was used to analyze all these proteins. CDC42EP4 protein results were included with DOCK5 in the top figure in the results since genes encoding for both these were found to be upregulated in our RNA Seq findings. p38 and S6k1 were quantified as pertinent proteins in the signaling pathways downstream of CDC42. , 
 Thank you. The same blot can be reprobed but (as you may be losing antigen or leaving artifacts) this should be noted in the method or legend. ,