ASMA BRONCHIALE E RINITE ALLERGICA: RUOLO DEL RECETTORE ST2 SUI LINFOCITI T HELPER 2

Bronchial Asthma and Allergic Rhinitis: Role of ST2 receptor on T helper 2 lymphocytes.

Introduction: T helper 2 (Th2) lymphocytes play an important role in the chronic inflammatory process concerning bronchial asthma and allergic rhinitis (1), regulating the production of some new cytokines, IL-17A and IL-33 with ST2 receptor, selectively expressed on the Th2 cells surface (2, 3), by the airway epithelium. IL-17A and IL-33 are involved in the Th2 cells-mediate induction of the bronchial and nasal mucosa inflammation, triggering the production of more inflammatory cytokines, including IL-31 (4).
Materials and Methods: Plasma samples from allergic rhinitis, both asthma and rhinitis patients and control subjects were collected. These subjects were recruited for this study following pathophysiological history, preliminary interview, spirometry and Prick Test. Plasma concentrations of IL-31, IL-33 and IL-17A were measured by ELISA. Also, IL-17A, IL-31 and ST2 receptor were evaluated by flow cytometric analysis on peripheral blood mononuclear cells (PBMC) of some of these patients. After all, the in vitro activity of a steroidal drug, Beclomethasone Dipropionate (BDP) (10−8M e 10−7M), was evaluated on the intracellular cytokines IL-17A and IL-31 expression, together with ST2 receptor levels in PBMCs cultures.
Results: IL-17A, IL-31 e IL-33 plasma levels were significantly higher in patients with allergic rhinitis and in those with both asthma and rhinitis than in control subjects. Flow cytometer data show that the expression of the intracellular cytokines IL-31 and IL-17A were increased in all patients categories compared to controls. At the same time, ST2 receptor expression levels, on T cells surface of these same patients, were significantly lower than those in control subjects. Finally, has been observed that BDP substantially decreases intracellular levels of IL-17A and IL-31 cytokines in PBMCs of these patients compared to baseline. Rather, the ST2 receptor surface expression was increased in a dose-dependent manner and, significantly, at BDP concentration 10-7M.
Conclusions: In the present study, the experimental data suggest that there is a correlation between higher levels of IL-17A, activation of IL-33/ST2 axis and increased concentration of IL-31 in bronchial asthma and allergic rhinitis and that these three new cytokines could therefore represent valid biomarkers evaluable in the pathogenesis and diagnosis of both diseases. At last, the results of this study supported the potential therapeutic approach by BDP in local and systemic inflammation control, of Th2 and Th17 immune response, in patients with inflammatory diseases of allergic airways.
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