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Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells

 Jae-Uoong Shim  ;  Shee Eun Lee  ;  Won Hwang  ;  Changhon Lee  ;  Jung-Won Park  ;  Jung Ho Sohn  ;  Jong Hee Nam  ;  Young Kim  ;  Joon Haeng Rhee  ;  Sin-Hyeog Im  ;  YoungIl Koh 
 Journal of Allergy and Clinical Immunology, Vol.137(2) : 426-435, 2016 
Journal Title
 Journal of Allergy and Clinical Immunology 
Issue Date
Adoptive Transfer ; Allergens/immunology ; Animals ; Asthma/genetics ; Asthma/immunology* ; Asthma/metabolism* ; Asthma/pathology ; Asthma/therapy ; Case-Control Studies ; Dendritic Cells/immunology* ; Dendritic Cells/metabolism ; Disease Models, Animal ; Female ; Flagellin/immunology* ; Immunomodulation* ; Ligands ; Mice ; Mice, Knockout ; Ovalbumin/immunology ; Pyroglyphidae/immunology ; T-Lymphocytes, Regulatory/immunology* ; T-Lymphocytes, Regulatory/metabolism ; Toll-Like Receptor 5/genetics ; Toll-Like Receptor 5/metabolism
Asthma ; Toll-like receptor 5 ; dendritic cells ; flagellin ; regulatory T cells
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. CONCLUSION: These findings collectively suggest that flagellin could be used as a tolerogenic adjuvant to treat allergic asthma.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
박중원(Park, Jung Won) ORCID logo https://orcid.org/0000-0003-0249-8749
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