IL-17 eliminates therapeutic effects of oral tolerance in murine airway allergic inflammation

Clin Exp Allergy. 2012 Jun;42(6):946-57. doi: 10.1111/j.1365-2222.2012.04006.x.

Abstract

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 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.

MeSH terms

  • Administration, Oral
  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Asthma / immunology*
  • Asthma / therapy*
  • CD4-Positive T-Lymphocytes / immunology
  • Desensitization, Immunologic*
  • Eosinophilia / immunology
  • Female
  • Immune Tolerance* / drug effects
  • Interleukin-17 / administration & dosage
  • Interleukin-17 / immunology*
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / immunology
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peyer's Patches / immunology
  • Th17 Cells / immunology*
  • Th2 Cells / immunology

Substances

  • Antibodies, Monoclonal
  • Interleukin-17
  • Interleukin-6
  • Ovalbumin