TY - JOUR
T1 - Linking acute infection to chronic lung disease. The role of IL-33-expressing epithelial progenitor cells
AU - Holtzman, Michael J.
AU - Byers, Derek E.
AU - Brett, Jennifer Alexander
AU - Patel, Anand C.
AU - Agapov, Eugene
AU - Jin, Xiaohua
AU - Wu, Kangyun
N1 - Publisher Copyright:
Copyright © 2014 by the American Thoracic Society
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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.
AB - 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.
KW - Airway epithelial cell
KW - IL-13
KW - IL-33
KW - Innate immune response
KW - Progenitor/stem cell
UR - http://www.scopus.com/inward/record.url?scp=84919684903&partnerID=8YFLogxK
U2 - 10.1513/AnnalsATS.201402-056AW
DO - 10.1513/AnnalsATS.201402-056AW
M3 - Article
C2 - 25525734
AN - SCOPUS:84919684903
SN - 2325-6621
VL - 11
SP - S287-S291
JO - Annals of the American Thoracic Society
JF - Annals of the American Thoracic Society
ER -