title: Linking acute infection to chronic lung disease. The role of IL-33-expressing epithelial progenitor cells.
abstract: Respiratory infection is a common feature of the major human airway diseases, such as asthma and chronic obstructive pulmonary disease, but the precise link between acute infection and chronic lung disease is still undefined. In a mouse model of this process, parainfluenza virus infection is followed by long-term induction of IL-33 expression and release and in turn innate immune cell generation of IL-13 and consequent airway disease signified by excess mucus formation. IL-33 induction was traceable to a subset of secretoglobin-positive airway epithelial cells linked to progenitor/stem cell function. In corresponding studies of humans with chronic obstructive pulmonary disease, an increase in IL-33 production was also detected in concert with up-regulation of IL-13 and airway mucus formation. In this case, increased IL-33 production was localized to a subset of airway basal cells that maintain an endogenous capacity for increased pluripotency and ATP-regulated release of IL-33 even ex vivo. The results provide evidence of a sustainable epithelial cell population that may be activated by environmental danger signals to release IL-33 and thereby lead to IL-13-dependent disease. The progenitor nature of this IL-33-expressing ATP-responsive cell population could explain an acquired susceptibility to chronic airway disease. The findings may therefore provide a new paradigm to explain the role of viral infection and the innate immune system in chronic lung disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production. Further studies are needed to address the basis for this type of postviral reprogramming and the means to correct it and thereby restore airway mucosal immune function to normal.
authors.affiliation: Immunology Group, Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Holtzman
authors.forename: Derek E
authors.initials: DE
authors.lastname: Byers
authors.forename: Jennifer-Alexander
authors.initials: JA
authors.lastname: Brett
authors.forename: Anand C
authors.initials: AC
authors.lastname: Patel
authors.forename: Eugene
authors.initials: E
authors.lastname: Agapov
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jin
authors.forename: Kangyun
authors.initials: K
authors.lastname: Wu
mesh_terms: D000208:Acute Disease; D000818:Animals; D066026:Endothelial Progenitor Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007239:Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis*; D051379:Mice; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins
keywords: IL-13; IL-33; airway epithelial cell; innate immune response; progenitor/stem cell