title: Critical role of IL-6 in dendritic cell-induced allergic inflammation of asthma.
abstract: Interleukin (IL)-6 plays important roles in autoimmunity and inflammation and is essential for T helper (Th) 2 and Th17 differentiation. However, whether it is involved in the development and function of dendritic cells (DCs) during allergen-induced airway inflammation and airway hyper-reactivity (AHR) remains undefined. In this study, Dermatophagoides pteronyssinus (Der p)-induced airway inflammation and AHR were studied in IL-6 knockout (KO) mice. Der p-loaded bone marrow-derived DCs (BMDCs) from IL-6 KO mice were used to assaying their ability to induce airway inflammation in naïve wild-type mice. Our results showed that IL-6 KO mice showed reduced AHR, significant decreases in inflammatory cell recruitment and Th2 and Th17 cytokine production in the airways, and lowered Der p-specific immunoglobulin G1 after Der p exposure. Further exploration of BMDCs from IL-6 KO mice revealed decreased activity of phagocytosis and reduced expression of MHC class II and CD86 after Der p stimulation. Adoptive transfer of Der p-loaded BMDCs from IL-6 KO mice also showed a functional defect in their inability to induce Th2 and Th17 immune responses and trigger airway inflammation and AHR in recipient mice. Finally, in allergic asthmatics, DCs that differentiated from monocytes treated with anti-IL-6 receptor antibody (tocilizumab) had poor capacity for eliciting Th2 polarization as compared to DCs generated from monocytes without antibody treatment. In conclusion, IL-6 signaling in DCs is essential for their uptake of allergens, maturation, and initiation of Th2/Th17-mediated airway inflammation and AHR in asthma, thus providing a new potential target for treating allergic asthma.
  
  
  CONCLUSIONS
  IL-6 signaling is important for DCs to take up allergens and to initiate Th2/Th17-mediated airway inflammation. DCs from allergic asthmatics treated with anti-IL-6 receptor antibody had poor capacity for eliciting Th2 polarization. Anti-IL-6 treatment may provide a new potential target for treating allergic asthma.
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Institute of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shun-Hua
authors.initials: SH
authors.lastname: Chen
authors.affiliation: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. a122@mail.ncku.edu.tw.|Allergy and Clinical Immunology Research (ACIR) Center, College of Medicine, National Cheng Kung University, Tainan, Taiwan. a122@mail.ncku.edu.tw.|China Medical University Children Hospital, Taichung, Taiwan. a122@mail.ncku.edu.tw.|Department of Pediatrics, College of Medicine, National Cheng Kung University, Tainan, 70101, Taiwan. a122@mail.ncku.edu.tw.
authors.forename: Jiu-Yao
authors.initials: JY
authors.lastname: Wang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D051940:B7-2 Antigen / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D040002:Dermatophagoides pteronyssinus / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D039741:Antigens, Dermatophagoides; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C577686:interleukin-6, mouse; C502936:tocilizumab
keywords: Airway inflammation; Allergic asthma; Dendritic cells; Dermatophagoides pteronyssinus; IL-6