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. 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.
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. 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.
Authors: Gwen S Skloot; Paula J Busse; Sidney S Braman; Elizabeth J Kovacs; Anne E Dixon; Carlos A Vaz Fragoso; Nicola Scichilone; Y S Prakash; Christina M Pabelick; Sameer K Mathur; Nicola A Hanania; Wendy C Moore; Peter G Gibson; Susan Zieman; Betina B Ragless Journal: Ann Am Thorac Soc Date: 2016-11
Authors: Paula J Busse; Janette M Birmingham; Agustin Calatroni; Joseph Manzi; Anna Goryachokovsky; Giselle Fontela; Alex D Federman; Juan P Wisnivesky Journal: J Allergy Clin Immunol Date: 2016-10-08 Impact factor: 10.793
Authors: Seil Sagar; Kim A T Verheijden; Niki A Georgiou; Johan Garssen; Aletta D Kraneveld; Arjan P Vos; Gert Folkerts Journal: Mediators Inflamm Date: 2013-05-27 Impact factor: 4.711
Authors: C Gómez-Casado; M Garrido-Arandia; P Gamboa; N Blanca-López; G Canto; J Varela; J Cuesta-Herranz; L F Pacios; A Díaz-Perales; L Tordesillas Journal: Clin Dev Immunol Date: 2013-11-14
Authors: Seil Sagar; Mary E Morgan; Si Chen; Arjan P Vos; Johan Garssen; Jeroen van Bergenhenegouwen; Louis Boon; Niki A Georgiou; Aletta D Kraneveld; Gert Folkerts Journal: Respir Res Date: 2014-04-16