Nuclear IL-33 as a growth and survival agent within basal cells

• Published in: The Journal of clinical investigation Vol. 131; no. 19
• Main Author: Chapman, Harold A
• Format: Journal Article
• Language: English
• Published: American Society for Clinical Investigation 01.10.2021
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI153203

IL-33 is a well-studied cytokine that resides normally within nuclei but can be released by cell damage or stress to then signal via a single receptor widely expressed on immune cells to promote host resistance and type 2 allergic immunity. In this issue of the JCI, Wu et al. used a well-established model of mouse Sendai viral infection to show that IL-33 was induced in distal lung airway epithelium, specifically in cell-cycling basal cells. IL-33 induced cell-cycling basal cells to expand and migrate into the alveolar compartment, presumably to restore barrier function. However, restoring barrier function with airway-derived cells may also result in persistent alveolar metaplasia. Surprisingly, nuclear IL-33 in this system acted cell autonomously, independently of release and conventional ST2 (IL1RL1) receptor signaling. The findings uncover a signaling role for nuclear IL-33 in viral activation of mouse basal cells and add to the well-known "alarmin" function of IL-33.