STAT6 expression in T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects

Katsuyuki Tomita,Kazuhiro Ito,Peter J Barnes,Yuji Tohda,Timothy Oates,Hiroyuki Sano,K Fan Chung,Gaetano Caramori,Ian M Adcock,Borja Cosio,Sam Lim

doi:10.1186/1476-9255-9-5

Abstract

BackgroundAsthma is characterised by increased numbers of Th2-like cells in the airways and IgE secretion. Generation of Th2 cells requires interleukin (IL)-4 and IL-13 acting through their specific receptors and activating the transcription factor, signal transducer and activator of transcription 6 (STAT6). STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses.MethodsWe have investigated the expression of STAT6 in peripheral blood T-lymphocytes, alveolar macrophages and bronchial biopsies from 17 normal subjects and 18 mild-moderate steroid-naïve stable asthmatic patients.ResultsSTAT6 expression was variable and was detected in T-lymphocytes, macrophages and bronchial epithelial cells from all subjects with no difference between normal and stable asthmatic subjects.ConclusionsSTAT6 expression in different cells suggests that it may be important in regulating the expression of not only Th2-like cytokines in T cells of man, but may also regulate STAT-inducible genes in alveolar macrophages and airway epithelial cells.

Highlights

Asthma is characterised by chronic airway inflammation, with infiltration of T-lymphocytes, mast cells, eosinophils and monocytes/macrophages
In order to confirm the site of signal transducer and activator of transcription 6 (STAT6)-responsive gene expression and activation we have investigated the expression of STAT6 and phosphorylated STAT6 proteins in peripheral venous blood T cells, alveolar macrophages and bronchial biopsies of normal and asthmatic subjects using Western blotting and immunolocalisation
T-Lymphocytes Western blot analysis of isolated T cells showed no significant difference in the expression of STAT6 in steroidnaive asthmatic patients compared to normal subjects (0.73 ± 0.18 vs 0.72 ± 0.22; not significant) (Figure 1)

Summary

Introduction

Asthma is characterised by chronic airway inflammation, with infiltration of T-lymphocytes, mast cells, eosinophils and monocytes/macrophages. This is associated with the increased expression of several inflammatory proteins, including cytokines, enzymes, receptors and adhesion molecules [1]. CD4+ T helper (Th) cells can be divided into four major subsets termed Th1, Th2, Th17 and Th0 based on the pattern of cytokines they produce. Another two subsets of effector CD4+ Th cells, named Th9 and Th22 cells, have been described, even if their pathophysiological meaning is still unclear [5,6]. STAT6 knockout mice fail to produce IgE, airway hyperresponsiveness and bronchoalveolar lavage eosinophilia after allergen sensitisation, suggesting a critical role for STAT6 in allergic responses

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Conclusion