Forkhead box protein A2 and T helper type 2-mediated pulmonary inflammation

Abstract

The transcription factor forkhead box protein A2 (FOXA2, also known as hepatocyte nuclear factor 3β or transcription factor 3β), has been found to play pivotal roles in multiple phases of mammalian life, from the early development to the organofaction, and subsequently in homeostasis and metabolism in the adult. In the embryonic development period, FOXA2 is require d for the formation of the primitive node and notochord, and its absence results in embryonic lethality. Moreover, FOXA2 plays an important role not only in lung development, but also in T helper type 2 (Th2)-mediated pulmonary inflammation and goblet cell hyperplasia. In this article, the role of FOXA2 in lung development and Th2-mediated pulmonary inflammation, as well as in goblet cell hyperplasia, is reviewed. FOXA2 deletion in airway epithelium results into Th2-mediated pulmonary inflammation and goblet cell hyperplasia in developing lung. Leukotriene pathway and signal transducers and activators of transcription 6 pathway may mediate this inflammation through recruitment and activation of denditric cell during lung developments. FOXA2 is a potential treatment target for lung diseases with Th2 inflammation and goblet cell hyperplasia, such as asthma and chronic obstructive pulmonary disease.

Keywords: Forkhead box protein A2; T helper type 2 inflammation; Pulmonary; Development; Goblet cell hyperplasia

Core tip: The transcription factor forkhead box protein A2 (FOXA2) plays pivotal roles in embryonic development and organogenesis. Conditional deletion of FOXA2 in airway epithelial cells during the early stage of lung development will result in abnormal morphology of the lung and T helper type 2-mediated pulmonary inflammation. In addition, FOXA2 regulates the goblet cell differentiation during lung development and in pulmonary diseases such as asthma and chronic obstructive pulmonary disease. FOXA2 may be a new target for the treatment of lung disease.