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IL ‐17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation
Author(s) -
Kawakami H.,
Koya T.,
Kagamu H.,
Kimura Y.,
Sakamoto H.,
Yamabayashi C.,
Furukawa T.,
Sakagami T.,
Miyabayashi T.,
Hasegawa T.,
Suzuki E.,
Narita I.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.04006.x
Subject(s) - immunology , medicine , inflammation , ovalbumin , oral administration , cytokine , allergic inflammation , adoptive cell transfer , monoclonal antibody , eosinophilia , sensitization , antibody , immunotherapy , allergy , systemic administration , antigen , t cell , biology , immune system , pharmacology , in vivo , microbiology and biotechnology
Summary Background 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. Objective 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 (α IL ‐17Ab) to a murine allergic airway inflammation model were investigated. Methods Mice sensitized to and challenged with OVA , received OVA feeding, followed by OVA challenges. Transfer of Th17 cells, administration of IL ‐17 or α IL ‐17Ab were executed during OVA feeding. Airway hyperresponsiveness ( AHR ), airway inflammation, Th2 cytokine response and lung pathology were assessed. Results 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 α IL ‐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 F oxp3‐positive regulatory T (Treg) cells in lungs and P ayer'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.