Foxa2 programs Th2 cell-mediated innate immunity in the developing lung

Gang Chen, Huajing Wan, Fengming Luo, Liqian Zhang, Yan Xu, Ian Lewkowich, Marsha Wills-Karp, Jeffrey A. Whitsett

Research output: Contribution to journalArticle

Abstract

After birth, the respiratory tract adapts to recurrent exposures to pathogens, allergens, and toxicants by inducing the complex innate and acquired immune systems required for pulmonary homeostasis. In this study, we show that Foxa2, expressed selectively in the respiratory epithelium, plays a critical role in regulating genetic programs influencing Th2 cell-mediated pulmonary inflammation. Deletion of the Foxa2 gene, encoding a winged helix/forkhead box transcription factor that is selectively expressed in respiratory epithelial cells, caused spontaneous pulmonary eosinophilic inflammation and goblet cell metaplasia. Loss of Foxa2 induced the recruitment and activation of myeloid dendritic cells and Th2 cells in the lung, causing increased production of Th2 cytokines and chemokines. Loss of Foxa2-induced expression of genes regulating Th2 cell-mediated inflammation and goblet cell differentiation, including IL-13, IL-4, eotaxins, thymus and activation-regulated chemokine, Il33, Ccl20, and SAM pointed domain-containing Ets transcription factor. Pulmonary inflammation and goblet cell differentiation were abrogated by treatment of neonatal Foxa2 Δ/Δ mice with mAb against IL-4Rα subunit. The respiratory epithelium plays a central role in the regulation of Th2-mediated inflammation and innate immunity in the developing lung in a process regulated by Foxa2.

Original languageEnglish (US)
Pages (from-to)6133-6141
Number of pages9
JournalJournal of Immunology
Volume184
Issue number11
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Chen, G., Wan, H., Luo, F., Zhang, L., Xu, Y., Lewkowich, I., Wills-Karp, M., & Whitsett, J. A. (2010). Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. Journal of Immunology, 184(11), 6133-6141. https://doi.org/10.4049/jimmunol.1000223