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It has been long recognized that, in addition to its barrier function, the airway epithelium is also involved in modulating innate and adaptive immune responses. The recent discovery of TSLP''s function in Th2-mediated allergic responses has further reinforced the central position of the airway epithelium in pathogenesis of asthma. This paradigm justifies the development and use of in vitro cell models of the airway epithelium in asthma research and in drug development. [Copyright &y& Elsevier]

Gap junctions are documented in the human airway epithelium but the functional expression and molecular identity of their protein constituents (connexins, Cx) in the polarized epithelium is not known. To address this question, we documented the expression of a family of epithelial Cx (Cx26, Cx30, Cx30.3, Cx31, Cx31.1, Cx32, Cx37, Cx40, and Cx43) in primary human airway epithelial cells (AEC) grown on porous supports. Under submerged conditions, AEC formed a monolayer of airway cells whereas the air–liquid interface induced within 30–60 days AEC differentiation into a polarized epithelium for up to 6–9 months. Maturation of AEC was associated with the down-regulation of Cx26 and Cx43. The well-differentiated airway epithelium exhibited gap junctional communication between ciliated and between ciliated and basal cells. Interestingly, Cx30 was mostly present between ciliated cells whereas Cx31 was found between basal cells. These results are supportive of the establishment of signal-selective gap junctions with maturation of AEC, likely contributing to support airway epithelium function. These results lay the ground for studying the role of Cx-mediated cell–cell communication during repair following AEC injury and exploring Cx-targeted interventions to modulate the healing process. [ABSTRACT FROM AUTHOR]