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

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Antonella De Luca, Marilena Pariano, Barbara Cellini, Claudio Costantini, Valeria Rachela Villella, Shyam Sushama Jose, Melissa Palmieri, Monica Borghi, Claudia Galosi, Giuseppe Paolicelli, Luigi Maiuri, Jan Fric, Teresa Zelante
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.

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Teaser

De Luca et al. reveal the complexity of IL-17 signaling in Aspergillus lung infection and fungal allergy. The authors describe a pathogenic loop under conditions of IL-17RA disruption and pave the way for therapeutic strategies selectively targeting the IL-17F/IL-17RC axis.


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