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

Abstract

SummaryBackground 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 while 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 ÀDDC t (2 ÀDDCt method). ResultsThe mean values and standard deviation of FoxP3, GATA-3 and T-bet relative expression for control vs. asthma were 10.2AE6.8 vs. 4.8AE3.8, 2.4AE2.9 vs. 1.7AE0.9 and 3.3AE2.1 vs. 2.1AE1.5, 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.

Effect of aging on sputum inflammation and asthma control

“…Nonetheless, our groups of younger and aged patients received comparable doses of ICS, and no relationship was found between ICS and sputum neutrophils. Although previous studies provided an initial insight to features of airway inflammation in the aged, these reports did not match study populations for disease severity and intensity of treatment 14–15, 34–35 , did not specifically address the effect of aging on immune markers of inflammation 34 , or evaluate inner-city patients, a highly at-risk asthma population in the United States.…”

“…The underlying mechanisms for increased Treg cells with aging may include increased clonal expansion, in particular due to chronic viral infection (e.g., cytomegalovirus), increased IL-15 protein and receptor expression (promoting Treg development and maintenance), and decreased expression of pro-apoptotic molecules 76–78 . One study has specifically analyzed markers of peripheral Treg cells in aged asthma patients and reported decreased numbers compared to normal controls 34 . However, younger patients were not included for comparison.…”

Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma

“…Imbalances in Th responses can also be detected using Th-specific transcription factors: T-bet for Th1 cells, GATA-3 for Th2 cells, retinoic acid orphan receptor-γt (RORγt) for Th17 cells and forkhead box P3 (Foxp3) for Tregs [44]. Alterations in the expression and/or function of Th-specific transcription factors were associated with asthma pathogenesis [45,46]. …”

Correlation between the ratio of T-bet/GATA-3 and the levels of IL-4 and IFN-γ in patients with allergic asthma

“…The disease may significantly complicate life if treatment is not obtained or properly followed; therefore, allergic asthma has become a serious threat to public health as a major chronic disease. Recently, an imbalance between the expression of transcription factor T-box expressed in T cells (T-bet) and GATA-binding protein-3 (GATA-3) was reported in bronchial asthma, particularly in allergic asthma (4,5). Further research on the ratio of T-bet/GATA-3 would be helpful in understanding the etiology of asthma and developing immunotherapy methods.…”