IL-17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation
Article first published online: 23 MAY 2012
© 2012 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 42, Issue 6, pages 946–957, June 2012
How to Cite
Cite this as: H. Kawakami, T. Koya, H. Kagamu, Y. Kimura, H. Sakamoto, C. Yamabayashi, T. Furukawa, T. Sakagami, T. Miyabayashi, T. Hasegawa, E. Suzuki and I. Narita, Clinical & Experimental Allergy, 2012 (42) 946–957.
- Issue published online: 23 MAY 2012
- Article first published online: 23 MAY 2012
- Accepted manuscript online: 31 MAR 2012 09:25AM EST
- Manuscript Accepted: 22 FEB 2012
- Manuscript Revised: 18 FEB 2012
- Manuscript Received: 24 SEP 2011
- bronchial asthma;
- regulatory T cell;
Oral tolerance is a classically used strategy for antigen-specific systemic immunotherapy. However, the roles of IL-17 in modification of oral tolerance are not yet understood.
To define the effects of IL-17 on the modification of oral tolerance, the effects of transfer of Th17 cells, administration of IL-17 or anti-IL-17 antibody (αIL-17Ab) to a murine allergic airway inflammation model were investigated.
Mice sensitized to and challenged with OVA, received OVA feeding, followed by OVA challenges. Transfer of Th17 cells, administration of IL-17 or αIL-17Ab were executed during OVA feeding. Airway hyperresponsiveness (AHR), airway inflammation, Th2 cytokine response and lung pathology were assessed.
Administration of IL-17 as well as transfer of Th17 cells aggravated AHR and airway allergic inflammation as compared with the findings in mice subjected to OVA feeding alone, whereas administration of αIL-17Ab ameliorated AHR and airway eosinophilia. The effects of Th17 transfer were presumably attributable to augmentation of endogenous IL-6 production in gut. The number of Foxp3-positive regulatory T (Treg) cells in lungs and Payer's patches was increased in the OVA fed mice, whereas the number of these cells was decreased in the mice subjected to OVA feeding + Th17 cell transfer. Neutralization of IL-6 by monoclonal antibody in the mice subjected to OVA feeding + transfer of Th17 cells restored the effects of oral tolerance.
Conclusions and Clinical Relevance
These data suggest that IL-17 may inhibit the induction of tolerance to antigen through, at least in part augmenting IL-6 production, thereby suppressing the expansion of Treg cells.