FoxP3, GATA-3 and T-bet expression in elderly asthma

Abstract

Background Asthma is a chronic inflammatory disorder in which Th2, Th1 and suppressive T cells (Tregs) play a role. The transcription factor FoxP3 plays a role in Treg differentiation hile T-bet is important for Th1 and GATA-3 for Th2 differentiation from naïve T cells. Recent data show that age-related deregulation of Treg cells is a mechanism of senescence affecting several chronic diseases. It is crucial to understand the behaviour of these cell populations in asthma for elderly patients. Objective To evaluate FoxP3, GATA-3 and T-bet gene expression under basal conditions and after in vitro activation in a group of elderly asthmatic compared with age-matched healthy individuals. Methods Thirty-two elderly asthmatics and 17 healthy elderly individuals were selected. Serum total IgE was measured, and peripheral blood mononuclear cells (PBMCs) were isolated and stimulated in vitro with anti-CD3/anti-CD28, followed by mRNA isolation. After reverse transcription, real-time quantitative PCR was performed and relative quantification was determined 2 DDCt (2 DDCt method). Results The mean values and standard deviation of FoxP3, GATA-3 and T-bet relative expression for control vs. asthma were 10.2 6.8 vs. 4.8 3.8, 2.4 2.9 vs. 1.7 0.9 and 3.3 2.1 vs. 2.1 1.5, respectively. Healthy individuals showed significantly higher expression of FoxP3 and T-bet; asthmatics had a lower T-bet/GATA-3 ratio, higher serum IgE and a positive significant correlation between total IgE and GATA-3 expression. Conclusion and clinical relevance Elderly asthmatic patients have lower FoxP3 mRNA expression in PBMC, which can be associated with the sustained inflammatory process and with the decreased immune tolerance by Treg cells. The T-bet deficiency and the correlation of GATA-3 expression with the increase of IgE are characteristics of long-lasting asthma. Changes related to the immunosenescence process could provide an explanation for the minor differences observed between the groups. It is important to clarify persistent modifications in long-lasting asthma in the elderly and adequate future therapeutic approaches.