Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease.

Published

Journal Article

Chronic obstructive lung disease is characterized by persistent abnormalities in epithelial and immune cell function that are driven, at least in part, by infection. Analysis of parainfluenza virus infection in mice revealed an unexpected role for innate immune cells in IL-13-dependent chronic lung disease, but the upstream driver for the immune axis in this model and in humans with similar disease was undefined. We demonstrate here that lung levels of IL-33 are selectively increased in postviral mice with chronic obstructive lung disease and in humans with very severe chronic obstructive pulmonary disease (COPD). In the mouse model, IL-33/IL-33 receptor signaling was required for Il13 and mucin gene expression, and Il33 gene expression was localized to a virus-induced subset of airway serous cells and a constitutive subset of alveolar type 2 cells that are both linked conventionally to progenitor function. In humans with COPD, IL33 gene expression was also associated with IL13 and mucin gene expression, and IL33 induction was traceable to a subset of airway basal cells with increased capacities for pluripotency and ATP-regulated release of IL-33. Together, these findings provide a paradigm for the role of the innate immune system in chronic disease based on the influence of long-term epithelial progenitor cells programmed for excess IL-33 production.

Full Text

Cited Authors

  • Byers, DE; Alexander-Brett, J; Patel, AC; Agapov, E; Dang-Vu, G; Jin, X; Wu, K; You, Y; Alevy, Y; Girard, J-P; Stappenbeck, TS; Patterson, GA; Pierce, RA; Brody, SL; Holtzman, MJ

Published Date

  • September 2013

Published In

Volume / Issue

  • 123 / 9

Start / End Page

  • 3967 - 3982

PubMed ID

  • 23945235

Pubmed Central ID

  • 23945235

Electronic International Standard Serial Number (EISSN)

  • 1558-8238

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/JCI65570

Language

  • eng