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, Young Il Koh

Research output: Contribution to journalArticle

27 Citations (Scopus)

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. Conclusion These findings collectively suggest that flagellin could be used as a tolerogenic adjuvant to treat allergic asthma.

Original languageEnglish
Pages (from-to)426-435
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number2
DOIs
Publication statusPublished - 2016 Feb 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells'. Together they form a unique fingerprint.

  • Cite this

    Shim, J. U., Lee, S. E., Hwang, W., Lee, C., Park, J. W., Sohn, J. H., Nam, J. H., Kim, Y., Rhee, J. H., Im, S. H., & Koh, Y. I. (2016). Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells. Journal of Allergy and Clinical Immunology, 137(2), 426-435. https://doi.org/10.1016/j.jaci.2015.07.010