Expression Of T Cell-specific Transcription Factors T-bet And GATA-3 In Chronic Urticaria

Objective: Chronic uticaria is a common allergic disease of dermatology, characteristic by reoccurring itching and wheal. But its' pathogenesis remain unclear. Recent studies showed that functional disorders of T helper lymphocyte subpopulation have close relationship with allergic diseases helper lymphocyte is divided into two functional subgroup,Th1and Th2.Th1secrete IFN-γ,IL-2 and other cytokine, mainly participates cellular immune.Th2 secret IL-4,IL-5,IL-13 and other cytokine, mainly takes part in humeral immune. Th1 and Th2 polarization is the key path of the immune response, Th1 and Th2 can inhibit each other and maintain dynamic balance in human body. Th1 and Th2 polarization disorder or defect can lead to disease. Some studies found that there was low expression of IFN-γand high expression of IL-4 in chronic urticaria patients, suggesting that there is misbalance of T helper lymphocyte subpopulation in chronic urticaria. The T box transcription factor T-bet (T-box expressed in T cells), newly discovered Th1 specific transcription factor, is expressed preferentially in Th1 cells. T-bet directly activated the endogenous IFN-γgene. In addition, although retroviral expression of T-bet in CD4 T cells undergoing Th2 cell differentiation can induce IFN-γ expression, including chromatin remodeling of signature genes. Thus, T-bet induces an IFN-γproducing Th1 phenotype, and meanwhile also represses IL-4 and IL-5 production from differentiated Th2 cells. GATA-3 (GATA-binding protein-3) is a member of the zincfinger family of transcription factors, which specificly induces Th2 differentiation and suppresses Th1 differentiation. In differentiated Th2 cells, GATA-3 is necessary for the expression of all of Th2 cytokines. Remarkably, retroviral gene transduction of GATA-3 into polarized Th1 and Tc1 primary T cells redirects them into Th2 and Tc2 cells, respectively. Accordingly, the specific transcription factors T-bet and GATA-3 are critical reciprocal determinants of Th1 and Th2 cell differentiation. In addition, it has substituted the former cytokine pattern.Thirty-three chronic urticaria(CU)patients and 20 controls were enrolled in this study. Our study aimes to investigate the expression and significance of T-bet and GATA-3 in CU and to observe the effect of the ratio of transcription factors T-bet/GATA-3 on the imbalance Th1 /Th2 cell. Further, from the Transcription level to elaborate the pathogenesis of chronic urticaria. To explore whether the T-bet/GATA-3 as Specific targeting of this pathway may be a promising novel therapeutic means of manipulating Th1 and Th2 responses. It suggests a mechanism for switching between Th1 and Th2 in the so-called irreversible state that may be developed as a stronger, side effect smaller strategy for the treatment of patients with chronic urticaria .Methods: The case group involved thirty typical chronic urticaria patients who were selected in outpatient clinic in the second hospital of Hebei Medical University. Including standards: 1.All the patients are typical chronic urticaria patients. 2. Course of disease exceeds 8 cycles , the paroxysm is not weekly less than 2 time. 3. All the cases involved had not taken antihistamines for three days, astemizole for one month, or drugs that could affect immunological function for two months such as corticosteroids and immunosuppressive agent, et al. 4. Age between 18-60-year-old. Excluding standards: 1. Sensibiligen is food,medicine,the infection and so on. on clinical has explicitly sensitized reason. 2. patients with factitious urticaria,cold urticaria,cholinergic urticaria,solar urticaria,pressure urticaria,angioedema. 3. The pregnant woman and lactivorous woman. 4. patients with autoimmunity diseases such as erythema lupus,pemphigus,dermatomyositis,rheumatic arthritis et al, patients with tumor,other severe Systemic diseases or allergic diseases. The control group involved twenty healthy people without allergic diseases,autoimmunity diseases and family history. With respect to age,gender, there was not significant difference between the two groups by analysis of t-test.Peripheral venous blood 6ml were obtained from 33 cases with CU (patients group) and 20 normal cases( controls group), each to add EDTA 0.8ml for anticoagulation. Peripheral blood mononuclear cells (PBMC) were isolated by density gradient centrifugation from patients and healthy controls. Expressions of T-bet and GATA-3 in the PBMC were detected by reverse transcription-polymerase chain reaction (RT-PCR) respectively according to directions in the each reagent .Data were analysed using the Satistical Package of the SPSS14.0. The positive expression rate of T-bet and GATA-3 mRNA in CU patients and normal cases were tested by analysis of chi square test. The data means about expression of T-bet and GATA-3 mRNA in CU patients and normal cases was not mormal distribution and The data means were tested by analysis of analysis of variance, the result was heterogeneity of variance. Thus variables were tested by analysis of Wilcoxon rank sum test. The P-values of less than 0.05 being considered to be statistically significant.Results:1.The median of expression of T-bet mRNA were 18.70% in the chronic urticaria patients group,and were 28.55% in the control group. There was a significant difference between the two groups. (P=0.000);2. In the chronic urticaria patients, the median levels of GATA-3 mRNA expression were 58.48%, which was significantly increased compared with that in the control group 22.47%,(P=0.006);3. The ratio of T-bet/GATA-3 in the chronic urticaria patients group was significantly lower than those in the control group, There was a significant difference between the two groups.(P=0.025).Conclusion: 1. The expression of T-bet mRNA in the chronic urticaria patients group was significantly lower than those in the control group. On the contrary, The expression of GATA-3 mRNA in the chronic urticaria patients group was significantly increased compared with that in the control group . The result indicates that there was low expression of Th1 subset and high expression of Th2 subset in chronic urticaria. Imbalance of Th1/Th2 perhaps plays an important role in chronic urticaria.2. The ratio of T-bet/GATA-3 in the chronic urticaria patients group was significantly lower than those in the control group,Imbalance of transcription factors T-bet/GATA-3 may be one of the key factors in chronic urticaria. The general steps of the production of inflammation factors could be controlled at a transcriptional level by regulating the ratio of T-bet/GATA-3, so that could be to reverse the imbalance of Th1/Th2 , and it could be treated more effectively and lower adverse reaction.