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.

CONCLUSION:

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

• Authors: 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
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 137 Issue 2 Pg. 426-35 (Feb 2016) ISSN: 1097-6825 [Electronic] United States
• PMID: 26303344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Allergens
• Ligands
• Toll-Like Receptor 5
• Flagellin
• flaB flagellin
• Ovalbumin

Topics

• Adoptive Transfer
• Allergens (immunology)
• Animals
• Asthma (genetics, immunology, metabolism, pathology, therapy)
• Case-Control Studies
• Dendritic Cells (immunology, metabolism)
• Disease Models, Animal
• Female
• Flagellin (immunology)
• Immunomodulation
• Ligands
• Mice
• Mice, Knockout
• Ovalbumin (immunology)
• Pyroglyphidae (immunology)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Toll-Like Receptor 5 (genetics, metabolism)