title: Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells.
abstract: BACKGROUND
  Although the hygiene hypothesis suggests that microbial infections could subvert asthma and thus a microbial product might serve as a therapeutic adjuvant for asthma, the relationship between bacterial components and asthma is complex. Recently, low levels of flagellin, the Toll-like receptor (TLR) 5 ligand, have been reported to promote asthma.
  
  
  OBJECTIVE
  We show that a therapeutic dose of flagellin suppresses asthma and that the effect occurs through generating regulatory dendritic cells (rDCs) and regulatory T (Treg) cells.
  
  
  METHODS
  Ovalbumin (OVA)-induced wild-type and TLR5 knockout asthmatic mice were treated intranasally with a mixture of OVA and 10 μg of a flagellin B (FlaB; of Vibrio vulnificus). OVA/FlaB-treated rDCs were adoptively transferred to mice with OVA-induced asthma. Anti-CD25 mAb was used to deplete Treg cells. A mixture of house dust mite (HDM) and FlaB was used to treat mice with HDM-induced asthma. Blood CD14(+) monocyte-derived dendritic cells from HDM-sensitive asthmatic patients were treated with FlaB and incubated with autologous CD4(+) T cells.
  
  
  RESULTS
  An OVA/FlaB mixture ameliorated OVA-induced asthma by inhibiting TH1/TH2/TH17 responses in a TLR5-dependent manner through generating rDCs and Treg cells. The adoptive transfer of OVA/FlaB-treated dendritic cells inhibited OVA-induced asthma, whereas the depletion of CD25(+) cells eliminated the inhibitory effect. A similar effect of FlaB was observed in mice with HDM-induced asthma. In patients with HDM-sensitive asthma, FlaB-treated rDCs inhibited HDM-stimulated TH1/TH2 responses while enhancing Treg cells in an IL-10-dependent manner.
  
  
  CONCLUSIONS
  These findings collectively suggest that flagellin could be used as a tolerogenic adjuvant to treat allergic asthma.
authors: Division of Allergy, Asthma and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors: Jae-Uoong
authors: JU
authors: Shim
authors: Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Korea.
authors: Shee Eun
authors: SE
authors: Lee
authors: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea; Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Korea.
authors: Won
authors: W
authors: Hwang
authors: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Korea; Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, Korea.
authors: Changhon
authors: C
authors: Lee
authors: Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors: Jung-Won
authors: JW
authors: Park
authors: Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors: Jung-Ho
authors: JH
authors: Sohn
authors: Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors: Jong Hee
authors: JH
authors: Nam
authors: Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
authors: Young
authors: Y
authors: Kim
authors: Clinical Vaccine R&D Center, National Research Laboratory of Molecular Microbial Pathogenesis, Research Institute for Vibrio Infections, Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea. Electronic address: jhrhee@chonnam.ac.kr.
authors: Joon Haeng
authors: JH
authors: Rhee
authors: Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Korea; Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, Korea. Electronic address: iimsh@postech.ac.kr.
authors: Sin-Hyeog
authors: SH
authors: Im
authors: Division of Allergy, Asthma and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. Electronic address: yikoh@jnu.ac.kr.
authors: Young-Il
authors: YI
authors: Koh
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005408:Flagellin / Q000276:immunology*; D056747:Immunomodulation; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D039981:Pyroglyphidae / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism
chemical_list: D000485:Allergens; D008024:Ligands; D051198:Toll-Like Receptor 5; D005408:Flagellin; C416532:flaB flagellin; D010047:Ovalbumin
keywords: Asthma; Toll-like receptor 5; dendritic cells; flagellin; regulatory T cells