Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells.

Imperatorin is a furanocoumarin compound which exists in many medicinal herbs and possesses various biological activities. Herein, we investigated the antiallergic effects of imperatorin in asthmatic mice and explored the immunomodulatory actions of imperatorin on immune cells. We used a murine model of ovalbumin (OVA)-induced asthma to evaluate the therapeutic potential of imperatorin. Additionally, bone marrow-derived dendritic cells (DCs; BMDCs) were used to clarify whether imperatorin exerts an antiallergic effect through altering the ability of DCs to regulate T cells. Oral administration of imperatorin to OVA-sensitized and -challenged mice decreased serum OVA-specific immunoglobulin E (IgE) production, attenuated the airway hyperresponsiveness (AHR), and alleviated airway inflammation in a dose-dependent manner. Notably, secretions of Th2 cytokines and chemokines were reduced, and numbers of interleukin (IL)-10-producing regulatory T cells (Tregs) increased in imperatorin-treated mice. Imperatorin inhibited proinflammatory cytokines and IL-12 production but enhanced IL-10 secretion by lipopolysaccharide (LPS)-stimulated BMDCs. Compared to fully mature DCs, imperatorin-treated DCs expressed high levels of the inducible costimulatory ligand (ICOSL) and Jagged1 molecules, and had the regulatory capacity to promote the generation of IL-10-producing CD4(+) T cells in vitro. Additionally, imperatorin directly suppressed activated CD4(+) T-cell proliferation and cytokine production. Imperatorin may possess therapeutic potential against Th2-mediated allergic asthma not only via stimulating DC induction of Tregs but also via direct inhibition of Th2 cell activation. These findings provide new insights into how imperatorin affects the Th2 immune response and the development of imperatorin as a Treg-type immunomodulatory agent to treat allergic asthma.

Lin CL ，Hsiao G ，Wang CC ，Lee YL ... -  《-》

Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice.

Zerumbone is a sesquiterpene compound isolated from the rhizome of wild ginger, Zingiber zerumbet Smith. The rhizomes of the plant are used as a spice and traditional medicine. Zerumbone was shown to possess anticarcinogenic, anti-inflammatory, and antioxidant properties. However, the antiallergic activity and the underlying mechanism of zerumbone have not been reported. Herein, we investigated the immunomodulatory effects of zerumbone on antigen-presenting dendritic cells (DCs) in vitro and its potential therapeutic effects against ovalbumin (OVA)-induced T helper 2 (Th2)-mediated asthma in mice. In the presence of zerumbone, lipopolysaccharide-activated bone marrow-derived DCs enhanced T cell proliferation and Th1 cell polarization in an allogeneic mixed lymphocyte reaction. In animal experiments, mice were sensitized and challenged with OVA, and were orally treated with different doses of zerumbone after sensitization. Circulating titers of OVA-specific antibodies, airway hyperresponsiveness to methacholine, histological changes in lung tissues, the cell composition and cytokine levels in bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were assessed. Compared to OVA-induced hallmarks of asthma, oral administration of zerumbone induced lower OVA-specific immunoglobulin E (IgE) and higher IgG2a antibody production, attenuated airway hyperresponsiveness, prevented eosinophilic pulmonary infiltration, and ameliorated mucus hypersecretion. Zerumbone treatment also reduced the production of eotaxin, keratinocyte-derived chemokine (KC), interleukin (IL)-4, IL-5, IL-10, and IL-13, and promoted Th1 cytokine interferon (IFN)-γ production in asthmatic mice. Taken together, these results suggest that zerumbone exhibits an antiallergic effect via modulation of Th1/Th2 cytokines in an asthmatic mouse model.

Shieh YH ，Huang HM ，Wang CC ，Lee CC ，Fan CK ，Lee YL ... -  《-》

Schisandrin B promotes Foxp3(+) regulatory T cell expansion by activating heme oxygenase-1 in dendritic cells and exhibits immunomodulatory effects in Th2-mediated allergic asthma.

Allergic asthma is induced by T helper 2 (Th2) responses and allergen-specific immunoglobulin E (IgE). In asthma, regulatory T (Treg) cells play a crucial role in controlling immune homeostasis, and induction of Treg cells is a good strategy to treat Th2-mediated allergic asthma. Schisandrin B (Sch B), the main component isolated from Schisandra chinensis, reportedly possesses various pharmacological properties, but its immunomodulatory mechanism in allergic asthma remains unclear. In the present study, we explored whether Sch B exerts an antiallergic effect through modifying the function of dendritic cells (DCs) to regulate T-cell polarization and further investigated the immunomodulatory effects of Sch B in allergic asthma. Herein, an in vitro study revealed that 20 μM of Sch B-treated bone-marrow-derived DCs exhibited a semi-mature phenotype that secreted low amounts of proinflammatory cytokines including interleukin (IL)-12, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and expressed decreased levels of surface molecules of cluster of differentiation 80 (CD80) and CD86. Compared to fully mature DCs, these Sch B-treated DCs displayed a regulatory ability to promote CD4+Foxp3+ Treg cell generation via upregulation of heme oxygenase (HO)-1 expression. Of note, in a murine model of ovalbumin (OVA)-induced asthma, levels of Th2-type cytokines such as IL-4, IL-5, and IL-13, and C-C motif chemokine 11 (CCL11) were dampened, whereas numbers of forkhead box P3 (Foxp3)-positive Treg cells were augmented in Sch B-treated mice. Moreover, administration of 5 mg/kg of Sch B alleviated the cardinal features of Th2-mediated allergic asthma, namely, serum OVA-specific IgE production, the development of airway hyperresponsiveness (AHR), and airway inflammation. Collectively, these findings indicate that the effectiveness of Sch B treatment against Th2-mediated allergic asthma was at least partially due to enhancement of DC induction of Treg cells, and Sch B can possibly be developed as an immunomodulatory adjuvant to treat allergic asthma.

Chiang CY ，Chang JH ，Chuang HC ，Fan CK ，Hou TY ，Lin CL ，Lee YL ... -  《-》

Administration of polysaccharides from Antrodia camphorata modulates dendritic cell function and alleviates allergen-induced T helper type 2 responses in a mouse model of asthma.

Liu KJ ，Leu SJ ，Su CH ，Chiang BL ，Chen YL ，Lee YL ... -  《-》

Staphylococcus succinus 14BME20 Prevents Allergic Airway Inflammation by Induction of Regulatory T Cells via Interleukin-10.

Song J ，Lim HX ，Lee A ，Kim S ，Lee JH ，Kim TS ... -  《-》