Osthole treatment ameliorates Th2-mediated allergic asthma and exerts immunomodulatory effects on dendritic cell maturation and function

Osthole,an active component of Chinese herbal medicines,reportedly possesses various pharmacological properties and has potential therapeutic applications.This study explored the anti-allergic effects of osthole in asthmatic mice and investigated the immunomodulatory actions of osthole on dendritic cells(DCs)and T cells.Herein,we show that oral administration of osthole to BALB/c mice after ovalbumin(OVA)sensitization ameliorated all of the cardinal features of T helper 2(Th2)-mediated allergic asthma;namely,the production of OVA-specific immunoglobulin E,airway hyperresponsiveness,airway inflammation and the production of Th2-type cytokines including interleukin(IL)-4,IL-5 and IL-13.Surprisingly,IL-10 production was not inhibited and was even enhanced by osthole treatment.We observed a significant increase in the percentages of IL-10-producing DCs and forkhead box P3-positive regulatory T(Treg)cells in osthole-treated asthmatic mice.Additionally,in vitro analyses revealed that osthole-treated bone-marrow-derived DCs had a partial maturation phenotype,secreting large amounts of IL-10 and low levels of proinflammatory cytokines,such as IL-12,IL-6 and tumor necrosis factor-α,and displaying reduced levels of MHC class II surface molecules.These DCs displayed immunosuppressive capacity by directly inhibiting effector T-cell responses or inducing Treg cells.In addition,osthole directly inhibited the activated CD4+T-cell proliferation and Th1/Th2-type cytokine production in this system.Collectively,these results suggest that DCs and T cells are potential target cells responsible for the action of osthole against allergic asthma.

Notch ligand-expressing adenovirus infection enhances the efficacy of dendritic cell-based immunotherapy for allergic asthma in mice

According to the World Health Organization,the prevalence of asthma is rising worldwide,and asthma causes 250,000 deaths annually.1 Allergic asthma is a type of chronic airway inflammation caused by dysregulated T helper type 2(Th2)-type immune responses.Patients with allergic asthma are characterized by elevated serum immunoglobulin E(IgE)antibody levels,mucus production,and pulmonary inflammation as well as airway hyperresponsiveness(AHR).2 Current therapeutic methods for asthma include inhaled corticosteroids andβ2 agonists to relieve asthma syndromes,but these treatments do not change the chronic disease course in patients.Some patients need high doses of inhaled corticosteroids or require long-term daily treatment with oral steroids.3 Therefore,efforts should be targeted towards developing innovative therapeutic strategies to improve patient quality of life and reduce unwanted deaths.One of the advances in the development of future therapies is the use of genetically modified dendritic cells(DCs)to decrease pathological Th2-mediated responses and maintain a disease-modifying effect long term.DC activation is crucial for inducing T cell immunity as well as determining T cell differentiation.4 Importantly,DCs can be cultured in vitro,and large amounts of generated clinical-grade DCs have become available.Additionally,DCs has been shown to be permissive of adenoviral(Ad)vector infection in vitro,and Ad vectors are a promising gene delivery platform for a variety of therapeutic and vaccine applications.5 In this regard,overexpressing immunoregulatory proteins in Ad-modified DCs would be an effective way to suppress Th2 cell immunity and establish an antiallergic response.