Acteoside exerts immunomodulatory effects on dendritic cells via aryl hydrocarbon receptor activation and ameliorates Th2-mediated allergic asthma by inducing Foxp3+ regulatory T cells

• Published in: International immunopharmacology 2022-05, Vol.106, p.108603-108603, Article 108603
• Main Authors: Chang, Jer-Hwa, Chuang, Hsiao-Chi, Hsiao, George, Hou, Tsung-Yun, Wang, Ching-Chiung, Huang, Shih-Chun, Li, Bo-Yi, Lee, Yueh-Lun
• Format: Article
• Language: English
• Subjects: Acteoside; Allergic asthma; Antigen-presenting cells; Antigens; Aromatic compounds; Asthma; Bone marrow; Bronchus; CD4 antigen; Cell activation; Cytokines; Dendritic cell; Dendritic cells; Forkhead protein; Foxp3 protein; Herbal medicine; Hydrocarbons; Immunoglobulin E; Immunomodulation; Immunoregulation; Inflammation; Interleukin 10; Interleukin 13; Interleukin 4; Interleukin 5; Lavage; Lipopolysaccharides; Lymphocytes; Lymphocytes T; Medicinal plants; Oral administration; Ovalbumin; Pathogenesis; Receptor mechanisms; Receptors; T cell; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.108603

[Display omitted] •Acteoside enhances IL-10 production by DCs via activation of the aryl hydrocarbon receptor.•Acteoside acts on DCs to promote the differentiation of Foxp3+ regulatory T cells.•Acteoside alleviates the severity of syndromes of ovalbumin-induced allergic asthma.•Acteoside promotes Foxp3+ regulatory T cell expansion in an allergic asthma model. Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in directing T-cell responses and are involved in the pathogenesis of allergic asthma. Acteoside, an active phenylethanoid glycoside, is widely distributed in many medicinal plants. Herein, we explored the immunomodulatory effects of acteoside on bone marrow-derived DCs in vitro, and further investigated the immunosuppressive ability of acteoside to manipulate T helper type 2 (Th2)-mediated allergic asthma in mice. Following lipopolysaccharide activation, 50 μM of acteoside significantly reduced the production of proinflammatory mediators, including interleukin (IL)-12 and tumor necrosis factor (TNF)-α, whereas it enhanced secretion of the anti-inflammatory cytokine, IL-10, by DCs. However, these effects of acteoside on DCs were reversed by pretreatment with CH223191, an aryl hydrocarbon receptor (AhR) antagonist. Additionally, coculture of acteoside-treated DCs with CD4+ T cells promoted the generation of forkhead box P3-positive (Foxp3+) regulatory T cells (Tregs) via AhR activation. Using a murine asthma model, our results demonstrated that oral administration of 50 mg/kg of acteoside decreased levels of Th2-type cytokines, such as IL-4, IL-5, and IL-13, whereas the level of IL-10 and the frequency of CD4+Foxp3+ Tregs were augmented. Moreover, acteoside treatment markedly inhibited the elevated serum level of ovalbumin-specific immunoglobulin E, attenuated the development of airway hyperresponsiveness, and reduced inflammatory cell counts in bronchoalveolar lavage fluid. Additionally, histological results reveled that acteoside ameliorated pulmonary inflammation in asthmatic mice. Taken together, these results indicated that acteoside exhibits immunomodulatory effects on DCs and plays an anti-inflammatory role in the treatment of allergic asthma.