IL-17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation.
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 (αIL-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 αIL-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 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
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.
Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
H
H
Kawakami
T
T
Koya
H
H
Kagamu
Y
Y
Kimura
H
H
Sakamoto
C
C
Yamabayashi
T
T
Furukawa
T
T
Sakagami
T
T
Miyabayashi
T
T
Hasegawa
E
E
Suzuki
I
I
Narita
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003888:Desensitization, Immunologic; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects; D020381:Interleukin-17 / Q000008:administration & dosage / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D020381:Interleukin-17; D015850:Interleukin-6; D010047:Ovalbumin