IL-17 Receptor Signaling in the Lung Epithelium Is Required for Mucosal Chemokine Gradients and Pulmonary Host Defense against K. pneumoniae

Publication date: Available online 27 October 2016
Source:Cell Host & Microbe
Author(s): Kong Chen, Taylor Eddens, Giraldina Trevejo-Nunez, Emily E. Way, Waleed Elsegeiny, David M. Ricks, Abhishek V. Garg, Carla J. Erb, Meihua Bo, Ting Wang, Wei Chen, Janet S. Lee, Sarah L. Gaffen, Jay K. Kolls
The cytokine IL-17, and signaling via its heterodimeric IL-17RA/IL-17RC receptor, is critical for host defense against extracellular bacterial and fungal pathogens. Polarized lung epithelial cells express IL-17RA and IL-17RC basolaterally. However, their contribution to IL-17-dependent pulmonary defenses in vivo remains to be determined. To address this, we generated mice with conditional deletion of Il17ra or Il17rc in Scgb1a1-expressing club cells, a major component of the murine bronchiolar epithelium. These mice displayed an impaired ability to recruit neutrophils into the airway lumen in response to IL-17, a defect in bacterial clearance upon mucosal challenge with the pulmonary pathogen Klebsiella pneumoniae, and substantially reduced epithelial expression of the chemokine Cxcl5. Neutrophil recruitment and bacterial clearance were restored by intranasal administration of recombinant CXCL5. Our data show that IL-17R signaling in the lung epithelium plays a critical role in establishing chemokine gradients that are essential for mucosal immunity against pulmonary bacterial pathogens.

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Teaser

IL-17 plays key roles in host defense, but the target cells in the lung are unclear. Chen et al. show that pulmonary epithelial IL-17R signaling is essential for regulating chemokine gradients, neutrophil recruitment, and bacterial clearance in the lungs. Epithelial administration of an IL-17R agonist may benefit patients with pneumonia.


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