Epithelium: at the interface of innate and adaptive immune responses

Abstract

Several diseases of the airways have a strong component of allergic inflammation in their cause, including allergic rhinitis, asthma, polypoid chronic rhinosinusitis, eosinophilic bronchitis, and others. Although the roles played by antigens and pathogens vary, these diseases have in common a pathology that includes marked activation of epithelial cells in the upper airways, the lower airways, or both. Substantial new evidence indicates an important role of epithelial cells as both mediators and regulators of innate immune responses and adaptive immune responses, as well as the transition from innate immunity to adaptive immunity. The purpose of this review is to discuss recent studies that bear on the molecular and cellular mechanisms by which epithelial cells help to shape the responses of dendritic cells, T cells, and B cells and inflammatory cell recruitment in the context of human disease. Evidence will be discussed that suggests that secreted products of epithelial cells and molecules expressed on their cell surfaces can profoundly influence both immunity and inflammation in the airways.

FIG 1

Model summarizing the influence of epithelial cells on innate and adaptive immune responses in the airways. Epithelial cells express pattern-recognition receptors and release antimicrobial products into the airways. They also interact with interepithelial DCs and subepithelial DCs to alter the ability of DCs to skew T cells. During inflammatory and immune responses, epithelial cells release specific chemokines that recruit subsets of granulocytes and T cells that are appropriate to the particular immune response. Finally, epithelial cells regulate the adaptive immune response by expression of soluble and cell-surface molecules that alter the function of DCs, T cells, and B cells in the airways. PAMP, Pathogen-associated molecular pattern; PRR, pathogen-recognition receptor; PMN, polymorphonuclear leukocyte; EOS, eosinophil; BASO, basophil; APRIL, a proliferation-inducing ligand.