Inactivation of the interleukin-22 pathway in the airways of cystic fibrosis patients. (January 2019)

• Record Type: Journal Article
• Authors: Guillon, Antoine; Brea, Deborah; Luczka, Emilie; Hervé, Virginie; Hasanat, Soujoud; Thorey, Camille; Pérez-Cruz, Magdiel; Hordeaux, Juliette; Mankikian, Julie; Gosset, Philippe; Coraux, Christelle; Si-Tahar, Mustapha
• Is Part Of: Cytokine. Volume 113(2019)
• Page Start: 470
• Page End: 474
• Publication Date: 2019-01
• Subjects: IL-22 -- Pseudomonas aeruginosa -- Cystic fibrosis -- Respiratory infection -- Neutrophil proteases; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.10.015
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-22 pathway is determinant to prevent P. aeruginosa –induced lung damage. IL-22 signaling is functional in ex-vivo airway epithelia of CF patients. IL-22 is rapidly and completely degraded by neutrophil proteases ( i.e. protease-3). We suspect an acquired deficiency of the IL-22 pathway in the lungs of CF patients. Abstract: Interleukin (IL)-22 plays a critical role in regulating the maintenance of the mucosal barrier. As airway epithelial regeneration is abnormal in cystic fibrosis (CF), we investigated IL-22 integrity in CF. We first demonstrated, using Il-22-/- mice, that IL-22 is important to prevent lung damage induced by the CF pathogen Pseudomonas aeruginosa . Next, IL-22 receptor was found normally expressed at the airway epithelial surfaces of CF patients. In wound-healing assays, IL-22-treated CF cultures had higher wound-closure rate than controls, suggesting that IL-22 signaling per se could be functional in a CF context. However, persistence of neutrophil-derived serine-proteases is a major feature of CF airways. Remarkably, IL-22 was found altered in this protease-rich inflammatory microenvironment; the serine protease-3 being the most prone to fully degrade IL-22. Consequently, we suspect an acquired deficiency of the IL-22 pathway in the lungs of CF patients due to IL-22 cleavage by the surrounding neutrophil serine-proteases.