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

Gang Chen1, Huajing Wan, Fengming Luo

  • 1Section of Neonatology, Perinatal and Pulmonary Biology, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 21, 2010
PubMed
Summary
This summary is machine-generated.

The transcription factor Foxa2, found in respiratory epithelial cells, is crucial for controlling lung inflammation. Its absence leads to spontaneous allergic airway inflammation and mucus production in mice.

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Area of Science:

  • Pulmonary immunology
  • Respiratory epithelial biology
  • Transcription factor regulation

Background:

  • The respiratory tract requires robust immune systems for homeostasis against environmental exposures.
  • Foxa2 is a transcription factor selectively expressed in the respiratory epithelium.

Purpose of the Study:

  • To investigate the role of Foxa2 in regulating Th2 cell-mediated pulmonary inflammation.
  • To understand the impact of Foxa2 deletion on lung immune responses and epithelial cell differentiation.

Main Methods:

  • Foxa2 gene deletion in mouse respiratory epithelial cells.
  • Analysis of lung inflammation, immune cell infiltration, and cytokine/chemokine production.
  • Gene expression profiling to identify regulated pathways.
  • In vivo blockade of IL-4Ralpha signaling.

Main Results:

  • Foxa2 deletion caused spontaneous pulmonary eosinophilic inflammation and goblet cell metaplasia.
  • Loss of Foxa2 led to increased recruitment and activation of myeloid dendritic cells and Th2 cells.
  • Upregulation of Th2 cytokines (IL-13, IL-4) and chemokines (eotaxins, thymus and activation-regulated chemokine) was observed.
  • Pulmonary inflammation and goblet cell changes were reversed by anti-IL-4Ralpha antibody treatment.

Conclusions:

  • Foxa2 is a critical regulator of Th2-mediated pulmonary inflammation and airway epithelial cell responses.
  • The respiratory epithelium, through Foxa2, plays a central role in innate immunity and allergic inflammation in the developing lung.