Differential expression of mRNA for Th1 and Th2 cytokine-associated transcription factors and suppressors of cytokine signalling in peripheral blood mononuclear cells of patients with atopic dermatitis

Abstract

Atopic dermatitis is characterized by Th2-dominant immunity. Recently many intracellular molecules have been reported to regulate cytokine expression and T cell differentiation. GATA-3 and T-box expressed in T cells (T-bet) are transcription factors that play a critical role in the development of Th2 and Th1 immunity, respectively. Suppressor of cytokine signalling (SOCS)-3 and SOCS-5, are negative regulators of the cytokine signalling induced by IL-12 and IL-4, respectively. Txk is a transcription factor that activates IFN-gamma gene directly. The present study was designed to identify intracellular molecules that are responsible for the pathogenesis and the imbalance of cytokines in atopic dermatitis. Semi-quantitative RT-PCR revealed that in peripheral blood mononuclear cells without any stimulation the levels of mRNA for GATA-3 and SOCS-3 were elevated, the levels of mRNA for Txk were depressed and the levels of mRNA for T-bet and SOCS-5 were comparable in patients with atopic dermatitis as compared with healthy controls. In addition, successful therapy normalized levels of mRNA for GATA-3 and Txk, although those for the others including IL-4, IL-5, IL-10, IL-13 and IFN-gamma did not change. Levels of Txk mRNA correlated with those of IFN-gamma, while the mRNA levels of the other regulators did not correlate with those of any of the cytokines. These results suggest GATA-3 and Txk might be involved in skin lesions, while SOCS-3 might be associated with an imbalance of cytokines that is difficult to normalize in atopic dermatitis.

Fig. 1

Relative levels of expression of mRNAs for (a) GATA-3, (b) T-bet, (c) SOCS-3, (d) SOCS-5 and (e) Txk in PBMCs from patients with atopic dermatitis (AD), from patients with non-atopic dermatoses with eosinophilia (Eo) and from healthy controls (HC). Horizontal bars indicate medians. Paired comparisons were evaluated by Mann-Whitney's U-test. NS, not significant.

Fig. 2

Relative levels of mRNAs for (a) GATA-3, (b) T-bet, (c) SOCS-3, (d) SOCS-5 and (e) Txk from patients with atopic dermatitis before and after therapy. Changes in symptom scores are shown in (f). Results were compared and evaluated using Wilcoxon's signed-ranks test. NS, not significant.

Fig. 3

The correlation between relative levels of the mRNA for Txk and the mRNA for IFN-γ.