ORIGINAL ARTICLE Intranasal Delivery of T-bet Modulates the Profi le of Helper T Cell Immune Responses in Experimental Asthma

Background: Allergic asthma is caused by aberrant helper T (TH) type 2 immune responses in susceptible individuals, characterized by airway hyperresponsiveness, chronic airway infl ammation, and mucus hypersecretion. Its prevalence continues to increase, but optimal treatment remains a challenge. The transcription factor T-bet is a master regulator of TH1 lineage commitment and strongly promotes interferon γ expression during TH1 cell differentiation. Objective: The aim of this study was to explore the role of intranasal delivery of T-bet on the differentiation of TH cell subsets and airway infl ammation in the ovalbumin (OVA)-induced mouse model of allergic airway infl ammation. Methods: BALB/c mice were sensitized by intraperitoneal injection of OVA and challenged with nebulized OVA. Four days before the inhalation challenge, the sensitized mice were subjected to intranasal delivery of a recombinant adeno-associated virus vector carrying murine T-bet gene (AAV-T-bet). Expression of the transcription factors T-bet, GATA3, and Foxp3 was then assayed in the lungs, and airway histology was analyzed along with other infl ammatory parameters, such as eosinophils and cytokines in bronchoalveolar lavage (BAL) fl uid, and total and OVA-specifi c immunoglobulin (Ig) E in serum. Results: Intranasal administration of AAV-T-bet effi ciently balanced the TH1/TH2 transcription factor and cytokine profi le and signifi cantly decreased the number of eosinophils in BAL fl uid. It also resulted in a reduction of peribronchial infl ammation scores and serum IgE levels in OVA-sensitized and challenged mice during the effector phase