The IL-17F/IL-17RC Axis Promotes Respiratory Allergy in the Proximal Airways

Cell Rep. 2017 Aug 15;20(7):1667-1680. doi: 10.1016/j.celrep.2017.07.063.

Abstract

The interleukin 17 (IL-17) cytokine and receptor family is central to antimicrobial resistance and inflammation in the lung. Mice lacking IL-17A, IL-17F, or the IL-17RA subunit were compared with wild-type mice for susceptibility to airway inflammation in models of infection and allergy. Signaling through IL-17RA was required for efficient microbial clearance and prevention of allergy; in the absence of IL-17RA, signaling through IL-17RC on epithelial cells, predominantly by IL-17F, significantly exacerbated lower airway Aspergillus or Pseudomonas infection and allergic airway inflammation. In contrast, following infection with the upper respiratory pathogen Staphylococcus aureus, the IL-17F/IL-17RC axis mediated protection. Thus, IL-17A and IL-17F exert distinct biological effects during pulmonary infection; the IL-17F/IL-17RC signaling axis has the potential to significantly worsen pathogen-associated inflammation of the lower respiratory tract in particular, and should be investigated further as a therapeutic target for treating pathological inflammation in the lung.

Keywords: ABPA; IL-17F/IL-17RC axis; Th17 immunity; allergy; respiratory infections.

MeSH terms

  • Animals
  • Aspergillosis / genetics
  • Aspergillosis / immunology*
  • Aspergillosis / microbiology
  • Aspergillosis / pathology
  • Aspergillus / immunology
  • Disease Models, Animal
  • Disease Susceptibility
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Hypersensitivity / microbiology
  • Hypersensitivity / pathology
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology*
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Protein Isoforms / immunology
  • Pseudomonas / immunology
  • Pseudomonas Infections / genetics
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / pathology
  • Receptors, Interleukin-17 / deficiency
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / immunology*
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / microbiology
  • Respiratory Mucosa / pathology
  • Signal Transduction
  • Staphylococcal Infections / genetics
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / immunology

Substances

  • Il17ra protein, mouse
  • Interleukin-17
  • Protein Isoforms
  • Receptors, Interleukin-17