Expression of Th1 and Th2 cytokine-associated transcription factors, T-bet and GATA-3, in peripheral blood mononuclear cells and skin lesions of patients with psoriasis vulgaris

Abstract

Psoriasis is considered as a T cell-mediated autoimmune disease, and the Th1 response has been established as the major immune agent in its pathomechanisms. The relative expression of Th1 and Th2 transcription factors, T-bet and GATA-3, resulting in a swing in the Th1/Th2 pendulum, has been implicated in a number of immunological diseases. However, their expression and correlation with psoriasis has not yet been studied. Our aim was to evaluate the expression of T-bet and GATA-3 in psoriatic patients and determine their correlation with serum levels of IFN-gamma and IL-4. Sera, peripheral blood mononuclear cells (PBMCs) and skin lesions were taken from 23 patients with psoriasis vulgaris. Serum levels of IFN-gamma and IL-4 were measured by ELISA. T-bet and GATA-3 mRNA expression in PBMCs was analyzed by RT-PCR. Lesional expression and distribution of CD4, CD8, T-bet and GATA-3 were assessed by immunohistochemistry. Blood and skin samples of healthy individuals served as controls. A markedly higher IFN-gamma and lower IL-4 concentration in the serum of psoriatic patients was found. A significantly higher expression of T-bet mRNA and a lower expression of GATA-3 mRNA in PBMCs, and consequently, a much higher T-bet/GATA-3 ratio in patients than in controls were shown. T-bet mRNA expression was strongly correlated with serum IFN-gamma secretion in patients; furthermore, the correlation between T-bet/GATA-3 ratio and IFN-gamma/IL-4 ratio was revealed. We also observed a significant increase in CD4+ cells and T-bet positive cells in psoriatic lesions. These results suggested that T-bet and GATA-3 might be regulator genes for psoriasis via the Th1/Th2 balance, and the Th1-specific transcription factor, T-bet, may play an important role in the development and maintenance of psoriasis.

Biochemical markers of psoriasis as a metabolic disease

“…Equally important immunological cells are Langerhans cells and dermal dendritic cells (dDC) (Figure 1). One of the immunological disturbances is the predominance of Th1 response [4][5][6]]. An elevated level of IFN-g, together with decreased levels of IL-4, fosters the inhibition of Th2 immune response [4,6].…”

“…One of the immunological disturbances is the predominance of Th1 response [4][5][6]]. An elevated level of IFN-g, together with decreased levels of IL-4, fosters the inhibition of Th2 immune response [4,6]. The leading role in the regulation of immune response in psoriasis is attributed to dendritic cells (DC).…”

Th1, Th2, Th17 and Regulatory T Cell Pattern in Psoriatic Patients: Modulation of Cytokines and Gene Targets Induced by Etanercept Treatment and Correlation with Clinical Response

“…The higher T-bet/GATA-3 ratio found in both skin and blood of psoriatic patients, together with markedly higher γ-interferon (IFN-γ) and lower interleukin (IL) 4 concentrations [4] well support the presence of an imbalance towards the Th1 response. Regulatory T (T reg ) cells were also reported to be both quantitatively and functionally deficient in their ability to suppress T cell activation [5,6,7].…”

Impact de l'interféron gamma sur la production de la kératine 15 dans les kératinocytes isolés de la peau de patients atteints d'épidermolyse bulleuse simplex /

“…Chez les sujets atteints, le niveau d'IFN-y est élevé. La cytokine régule l'expression du gène T-box transcription factor gene (T-bet) favorisant ainsi l'induction de la voie Thl (Zhu et al, 2010). Une étude a montré que l'IFN-y stimule l'expression des gènes KRT16 et KRT17 dans les kératinocytes humains en culture.…”