Gene expression in CD4⁺ T cells reflects heterogeneity in infant wheezing phenotypes

¹ Dep. of general paediatrics
² Dep. of dermatology
³ Dep. of paediatric pulmonology, Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands

^* To whom correspondence should be addressed. E-mail: m.o.hoekstra{at}umcutrecht.nl.

	Abstract

Although a marked increase in reporting of wheezing symptoms in the last few decades has been described, the underlying immunopathology of the different wheezing phenotypes is not clarified. Because differences in gene expression might be involved, our objective was to identify gene expression profiles in CD4⁺ T cells from two distinct infant wheezing phenotypes.

We compared gene expression profiles of peripheral CD4⁺ T cells by means of microarray of 6 transient wheezers, 6 persistent wheezers and 7 healthy controls. The genes differentially expressed were subsequently validated by RT-PCR.

The differential gene expression profiles reflect common immunological pathways involved in apoptosis or proliferation of T cells. Furthermore, both wheezing phenotypes show a decreased expression of complement 5 receptor (C5R1), a gene involved in the regulation of bronchial responsiveness. Moreover, differences in gene expression profiles were found in genes involved in the immune response against respiratory syncitial virus (RSV), such as signal transducer of transcription 1 (STAT1) and an inflammatory mediator with an enhanced production in asthma (prostaglandin E₂ receptor (Ptger2)).

Our findings suggest that clinical symptoms of wheezing are reflected in common immunological pathways, whereas differences between wheezing phenotypes are, partially, reflected in distinct gene expression profiles.