Expression Of T-bet And GATA-3 In Patients With Psoriasis Vulgaris

Psoriasis is a common chronic and inflammatory skin disorder with immunological based changes.In the past years,an increasing incidence has been noticed and most of the patients suffer a life-long disease.But up till now,the treatment is not satisfactory.Therefore,it can result in both physiological and psychological problems.Although the etiology of this disease is still unknown,it is believed that the psoriasis is a disease with a genetic susceptibility and T-cell-mediated immune disturbance.Researches have shown that Th1 cell differentiation and Th1 cytokine play an important role in the development and maintenance of psoriasis.Recently,it has been proved that both T-bet and GATA-3,as T cell differentiation-specific transcription factors,have determined the polarization differentiation of Th1 and Th2.As a member of the Tbr1 subfamily of T-box genes,T-bet plays a key role in Th1 cell differentiation.It not only controls the expression of IFN-γof Th1 specific cytokine,but also restrains the generation of IL-4 of Th2 specific ceil factor.Moreover,it also induces the shift of Th2 cell dominant toward the opposite Th1 cell dominant.So,T-bet has been confirmed as a unique Th1 specific transcription factor till now.However, GATA-3 promotes the generation of Th2 specific cell factor(such as IL-4 et al.),which is a Th2 specific transcription factor.Due to the important role of T-bet and GATA-3 in the process of Th cell differentiation,much attentions have been paid to their relation with the Th1 and Th2 driven diseases.Nowadays,the relationship between T-bet,GATA-3 and diseases such as asthma,inflammatory bowel disease, atopic dermatitis,rheumatoid arthritis,and so on has been studied. Recently,the expression of T-bet and GATA-3 by PBMC of psoriasis patients has been investigated by a group of Chinese scientists.However,the expression of T-bet/GATA-3 in skin lesions of psoriasis patients and their relationship with Th1/Th2 cytokines in the peripheral blood is not clear.In this study,cytokine secretion of IFN-γand IL-4 in peripheral blood and the expression of the specific transcription factors of T-bet and GATA-3 by PBMC and skin lesions of patients with psoriasis vulgaris were compared with normal controls.The aim of this investigation was to clarify the possible role of T-bet and GATA-3 in the pathogenesis of psoriasis.Materials and MethodsThe peripheral blood samples and skin tissues were obtained from active stage psoriasis patients in our hospital from September 2006 to March 2007.All the patients had no history of immune diseases,malignancy and other systemic diseases.No systemic treatment was accepted in the past month.All the biopsies were taken from newly developed lesions in two weeks without topical treatment.Normal controls were those receiving health care screening tests in our hospital whose complete blood count, urine analysis,stool analysis and biochemistry proved normal.ELISA was used to detect IFN-γand IL-4 level in peripheral blood of psoriasis patients and normal controls Expression of T-bet and GATA-3 by peripheral blood mononuclear cells and skin tissues of psoriasis patients and normal persons was analysed by RT-PCR and immunohistochemistry,respectively.Results1.IFN-γand IL-4 concentration in peripheral blood of patients with psoriasis vulgarisIFN-γconcentration in peripheral blood of 21 patients with psoriasis vulgaris was 16.20±2.00 pg/ml and 14.78±1.96 pg/ml of 20 normal controls. The difference between two groups was significant(P＜0.05).IL-4 concentration in peripheral blood of the patients was 22.12±6.70 pg/ml and 26.30±5.91 pg/ml of normal controls.Significant difference between the two groups was shown(P＜0.05).2.Expression of T-bet and GATA-3 in peripheral blood mononuclear cells of patients with psoriasis vulgarisExpression of T-bet in peripheral blood mononuclear cells of 21 patients with psoriasis vulgaris was significantly higher than that of normal controls(P＜0.05).However,the expression of GATA-3 in peripheral blood mononuclear cells of patients was significantly lower than that of normal controls(P＜0.05).3.Correlation analysis3.1 Correlation between expression of T-bet and IFN-γconcentrationIFN-γconcentration in peripheral blood was significantly correlated to the expression of T-bet in peripheral blood mononuclear cells in patients with psoriasis vulgaris,showing a correlation coefficient as 0.803(P＜0.05).It was noted that there was no correlation in the cases of low T-bet expression.However,a correlation was found in the cases of high T-bet expression.3.2 Correlation between expression of T-bet and IL-4 concentrationIL-4 concentration in peripheral blood was not correlated to the expression of T-bet in peripheral blood mononuclear cells in patients with psoriasis vulgaris,showing a correlation coefficient as-0.072(P＞0.05).3.3 Correlation between expression of GATA-3 and IFN-γconcentrationIFN-γconcentration in peripheral blood was not correlated to the expression of GATA-3 in peripheral blood mononuclear cells in patients with psoriasis vulgaris,showing a correlation coefficient as-0.5244 (P＞0.05).3.4 Correlation between expression of GATA-3 and IL-4 concentrationIL-4 concentration in peripheral blood was not correlated to the expression of GATA-3 in peripheral blood mononuclear cells in patients with psoriasis vulgaris,showing a correlation coefficient as 0.452 (P＞0.05).4.Comparison of the expression of CD4 and CD8 in skin lesions of patients with psoriasis vulgaris and normal human skin(1)The expression of CD4 was mainly on lymphocyte membrane in skin lesions of patients with psoriasis vulgaris.Most of the positive staining lymphocytes were in dermal papilla and the infiltrated lymphocytes in the epidermis.The expression of CD4 was also found in the normal human skin but sparse and weaker staining when compared with that in patients.The difference between the two groups was significant(P＜0.01).(2)The expression of CD8 was on lymphocyte membrane.The positive staining was only observed on lymphocytes in dermal papilla in skin lesions of patients with psoriasis vulgaris,rather than those lymphocytes infiltrated in the epidermis.The expression of CD8 was not found in the normal human skin.There was no significant difference between the two groups(P＞0.05).5.Comparison of the expression of T-bet and GATA-3 in skin lesions of patients with psoriasis vulgaris and normal human skin(1)The expression of T-bet was mainly in lymphocyte nucleus in skin lesions of patients with psoriasis vulgaris.Most positive lymphocytes were found in dermal papilla.Expression of T-bet was also found on part of the cell membrane of lymphocytes which were infiltrated in epidermis. Strongly positive staining of T-bet was mostly observed in most lymphocytes around the dialated blood vessels in dermal papilla.The expression of T-bet was not found in the normal human skin.There was a significant difference between the two groups(P＜0.01).Furthermore,the expression of T-bet was relatively higher in skin lesions showing strong CD4 expression,but the location and extension of expression of the two antibodies were different.(2)Only a few patients with psoriasis vulgaris showed a sporadic and weak expression of GATA-3 in lymphocyte nucleus in skin lesions.The same pattern of expression was found in a few normal controls.There was no significant difference between the two groups(P＞0.05).Conclusions1.Concentration of IFN-γin peripheral blood of patients with psoriasis vulgaris was higher than normal controls.But on the contrary,IL-4 was lower.It is proved that psoriasis have a Th1 cell dominant differentiation.2.Expression of T-bet in peripheral blood mononuclear cells of patients with psoriasis vulgaris was significantly higher than that of normal controls.The positive correlation between IFN-γconcentration in peripheral blood and expression of T-bet was significant.The expression of GATA-3 in peripheral blood mononuclear cells of patients with psoriasis vulgaris was significantly lower than that of normal controls.It was suggested that T-bet play an important role in the development and maintenance of psoriasis by a possible feedback loop together with IFN-γ,And GATA-3 might play a negative feedback role in psoriasis vulgaris.3.The expression of T-bet in skin lesions of patients with psoriasis vulgaris was significantly higher than that of normal controls. Furthermore,the expression level of T-bet was relatively higher in the skin lesions showing strong CD4 expression,but the location and extension of expression of the two antibodies were different.There was no significant difference between the expression of GATA-3 in skin lesions of patients with psoriasis vulgaris and normal controls.It is suggested that T-bet play an important role in the development of psoriasis,but not the unique crucial factor.