FoxP3, GATA-3 and T-bet expression in elderly asthma.
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 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(-ΔΔCt)(2(-ΔΔCt) 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.


CONCLUSIONS
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.
General Pathology Laboratory, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. spereira@fmed.uc.pt
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S
Vale-Pereira
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Todo-Bom
L
L
Geraldes
C
C
Schmidt-Weber
C A
CA
Akdis
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Mota-Pinto
D000368:Aged; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D050990:GATA3 Transcription Factor / Q000096:biosynthesis / Q000276:immunology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D008297:Male; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000098815:T-bet Transcription Factor
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007073:Immunoglobulin E