S'abonner

Flagellin suppresses experimental asthma by generating regulatory dendritic cells and T cells - 05/02/16

Doi : 10.1016/j.jaci.2015.07.010 
Jae-Uoong Shim, PhD a, , Shee Eun Lee, PhD b, , Won Hwang, MS c, g, , Changhon Lee, MS g, h, Jung-Won Park, MD d, Jung-Ho Sohn, MS d, Jong Hee Nam, MD e, Young Kim, MD, PhD e, Joon Haeng Rhee, MD, PhD f, , Sin-Hyeog Im, PhD g, h, , Young-Il Koh, MD, PhD a,
a Division of Allergy, Asthma and Clinical Immunology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea 
b Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Korea 
c School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea 
d Division of Allergy and Immunology, Department of Internal Medicine and Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea 
e Department of Pathology, Chonnam National University Medical School, Gwangju, Korea 
f 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 
g Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Korea 
h Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, Pohang, Korea 

Corresponding author: Joon Haeng Rhee, MD, PhD, Department of Microbiology, Chonnam National University Medical School, 5 Hak-Dong, Dong-Gu, Gwangju 501-190, Republic of Korea.Sin-Hyeog Im, PhD, Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Republic of Korea, Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang 790-784, Republic of Korea.Young-Il Koh, MD, PhD, Department of Internal Medicine, Chonnam National University Medical School, 42 Jebong-Ro, Dong-Gu, Gwangju 501-757, Republic of Korea.

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.

Le texte complet de cet article est disponible en PDF.

Key words : Asthma, Toll-like receptor 5, flagellin, dendritic cells, regulatory T cells

Abbreviations used : AHR, BALF, BMDC, DC, FlaB, Foxp3, HDM, LN, OVA, rDC, SIT, TLR, Treg, WT


Plan


 Supported by a grant of the Korean Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health and Welfare, Republic of Korea (HI14C0187). S.-H.I. was supported by grants from a research program by IBS-R005-G1-2015-a00.
 Disclosure of potential conflict of interest: The authors declare they have no relevant conflicts of interest.


© 2015  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
Ajouter à ma bibliothèque Retirer de ma bibliothèque Imprimer
Export

    Export citations

  • Fichier

  • Contenu

Vol 137 - N° 2

P. 426-435 - février 2016 Retour au numéro
Article précédent Article précédent
  • Characterization of acinar airspace involvement in asthmatic patients by using inert gas washout and hyperpolarized 3helium magnetic resonance
  • Sherif Gonem, Steven Hardy, Niels Buhl, Ruth Hartley, Marcia Soares, Richard Kay, Rino Costanza, Per Gustafsson, Christopher E. Brightling, John Owers-Bradley, Salman Siddiqui
| Article suivant Article suivant
  • The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis
  • Bojana Mirkovi?, Gillian M. Lavelle, Ahmed Abdul Azim, Kristine Helma, Fatma S. Gargoum, Kevin Molloy, Yael Gernez, Katie Dunne, Julie Renwick, Philip Murphy, Richard B. Moss, Catherine M. Greene, Cedric Gunaratnam, Sanjay H. Chotirmall, Noel G. McElvaney

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

Mon compte


Plateformes Elsevier Masson

Déclaration CNIL

EM-CONSULTE.COM est déclaré à la CNIL, déclaration n° 1286925.

En application de la loi nº78-17 du 6 janvier 1978 relative à l'informatique, aux fichiers et aux libertés, vous disposez des droits d'opposition (art.26 de la loi), d'accès (art.34 à 38 de la loi), et de rectification (art.36 de la loi) des données vous concernant. Ainsi, vous pouvez exiger que soient rectifiées, complétées, clarifiées, mises à jour ou effacées les informations vous concernant qui sont inexactes, incomplètes, équivoques, périmées ou dont la collecte ou l'utilisation ou la conservation est interdite.
Les informations personnelles concernant les visiteurs de notre site, y compris leur identité, sont confidentielles.
Le responsable du site s'engage sur l'honneur à respecter les conditions légales de confidentialité applicables en France et à ne pas divulguer ces informations à des tiers.


Tout le contenu de ce site: Copyright © 2024 Elsevier, ses concédants de licence et ses contributeurs. Tout les droits sont réservés, y compris ceux relatifs à l'exploration de textes et de données, a la formation en IA et aux technologies similaires. Pour tout contenu en libre accès, les conditions de licence Creative Commons s'appliquent.