PMID- 35123286 OWN - NLM STAT- MEDLINE DCOM- 20220406 LR - 20220406 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 106 DP - 2022 May TI - Acteoside exerts immunomodulatory effects on dendritic cells via aryl hydrocarbon receptor activation and ameliorates Th2-mediated allergic asthma by inducing Foxp3(+) regulatory T cells. PG - 108603 LID - S1567-5769(22)00087-X [pii] LID - 10.1016/j.intimp.2022.108603 [doi] AB - 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 muM of acteoside significantly reduced the production of proinflammatory mediators, including interleukin (IL)-12 and tumor necrosis factor (TNF)-alpha, 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. CI - Copyright (c) 2022 Elsevier B.V. All rights reserved. FAU - Chang, Jer-Hwa AU - Chang JH AD - Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Pulmonary Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Chuang, Hsiao-Chi AU - Chuang HC AD - School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan; Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. FAU - Hsiao, George AU - Hsiao G AD - Graduate Institute of Medical Sciences and Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Hou, Tsung-Yun AU - Hou TY AD - Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Rheumatology, Immunology and Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. FAU - Wang, Ching-Chiung AU - Wang CC AD - Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. FAU - Huang, Shih-Chun AU - Huang SC AD - Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Li, Bo-Yi AU - Li BY AD - School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. FAU - Lee, Yueh-Lun AU - Lee YL AD - Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: yllee@tmu.edu.tw. LA - eng PT - Journal Article DEP - 20220203 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Cytokines) RN - 0 (Forkhead Transcription Factors) RN - 0 (Foxp3 protein, mouse) RN - 0 (Glucosides) RN - 0 (Phenols) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 3TGX09BD5B (acteoside) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Animals MH - *Asthma/pathology MH - Bronchoalveolar Lavage Fluid MH - Cytokines/pharmacology MH - Dendritic Cells MH - Forkhead Transcription Factors MH - Glucosides MH - Mice MH - Mice, Inbred BALB C MH - Ovalbumin MH - Phenols MH - Receptors, Aryl Hydrocarbon MH - *T-Lymphocytes, Regulatory MH - Th2 Cells OTO - NOTNLM OT - Acteoside OT - Allergic asthma OT - Dendritic cell OT - T cell EDAT- 2022/02/06 06:00 MHDA- 2022/04/07 06:00 CRDT- 2022/02/05 20:17 PHST- 2021/10/22 00:00 [received] PHST- 2022/01/14 00:00 [revised] PHST- 2022/01/30 00:00 [accepted] PHST- 2022/02/06 06:00 [pubmed] PHST- 2022/04/07 06:00 [medline] PHST- 2022/02/05 20:17 [entrez] AID - S1567-5769(22)00087-X [pii] AID - 10.1016/j.intimp.2022.108603 [doi] PST - ppublish SO - Int Immunopharmacol. 2022 May;106:108603. doi: 10.1016/j.intimp.2022.108603. Epub 2022 Feb 3.