IL-27 suppresses Th2 cell development as well as Th2 cytokines production from polarized Th2 cells; a novel therapeutic way for Th2-mediated allergic inflammation.

抄録

IL-27/IL-27R shows up-regulatory effects on Th1 cells. Furthermore, IL-27 inhibits GATA-3, a transcription factor for Th2 cytokines, suggesting its high potential role in reciprocal regulation of Th1 and Th2 responses. Here, we demonstrated that IL-27 had a direct inhibitory effect on both the generation of Th2 cells and Th2 cytokines production from already polarized Th2 cells. Furthermore, we examined the possibility whether IL-27 shows strong therapeutic effects on Th2-induced allergic inflammation. BALB/c mice sensitized with OVA in Alum and challenged with intranasal administration of OVA developed airway hyperresponsiveness (AHR) in response to β-methacholine (Mch) exposure. They also showed typical peribronchial eosinophilic infiltration and mucous production by goblet cells. Daily ip injection of IL-27 (1 μg/day) for the first 7 days following immunization with OVA only modestly diminished AHR to Mch. In contrast, intranasal administration of IL-27 at the time of OVA challenge dose-dependently diminished AHR, airway eosinophilic inflammation and goblet cell metaplasia by diminishing IL-13 production in the lung. Thus, intranasal administration of IL-27 into OVA-immunized animals substantially diminishes IL-13 production by inhibition of Th2 cell generation and Th2 cytokines production, providing promising therapeutic way for the treatment of allergic asthma.