Glucocorticoids decrease Treg cell numbers in lungs of allergic mice

• Published in: European journal of pharmacology Vol. 747; pp. 52 - 58
• Main Authors: Olsen, P.C., Kitoko, J.Z., Ferreira, T.P., de-Azevedo, C.T., Arantes, A.C., Martins, Μ.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2015
• Subjects: Animals; Asthma; Asthma - drug therapy; Asthma - immunology; Cell Count; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Glucocorticoid; Glucocorticoids - pharmacology; Glucocorticoids - therapeutic use; Interleukin-10 - secretion; Lung - drug effects; Lung - immunology; Male; Mice; Ovalbumin - immunology; Pneumonia - drug therapy; Pneumonia - immunology; Pyroglyphidae - immunology; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - secretion; Thymus Gland - drug effects; Treg; Glucocorticoid; Treg; Asthma
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2014.11.034

Glucocorticoids have been the hallmark anti-inflammatory drug used to treat asthma. It has been shown that glucocorticoids ameliorate asthma by increasing numbers and activity of Tregs, in contrast recent data show that glucocorticoid might have an opposite effect on Treg cells from normal mice. Since Tregs are target cells that act on the resolution of asthma, the aim of this study was to elucidate the effect of glucocorticoid treatment on lung Tregs in mouse models of asthma. Allergen challenged mice were treated with either oral dexamethasone or nebulized budesonide. Broncoalveolar lavage and airway hyperresponsiveness were evaluated after allergenic challenge. Lung, thymic and lymph node cells were phenotyped on Treg through flow cytometry. Lung cytokine secretion was detected by ELISA. Although dexamethasone inhibited airway inflammation and hyperresponsiveness, improving resolution, we have found that both dexamethasone and budesonide induce a reduction of Treg numbers on lungs and lymphoid organs of allergen challenged mice. The reduction of lung Treg levels was independent of mice strain or type of allergen challenge. Our study also indicates that both glucocorticoids do not increase Treg activity through production of IL-10. Glucocorticoid systemic or localized treatment induced thymic atrophy. Taken together, our results demonstrate that glucocorticoids decrease Treg numbers and activity in different asthma mouse models, probably by reducing thymic production of T cells. Therefore, it is possible that glucocorticoids do not have beneficial effects on lung populations of Treg cells from asthmatic patients.