Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity

Abstract

It has become increasingly clear that airway epithelial cells are central participants in innate and adaptive immune responses as well as mucosal inflammation. Epithelial cells produce antimicrobial host defense molecules, proinflammatory cytokines and chemokines in response to activation via pathogen recognition receptors. Recruitment of immune cells including dendritic cells, T cells and B cells into the proximity of epithelium results in the enhancement of adaptive immunity through interactions with epithelial cells. Newly identified epithelial-derived cytokines, including TSLP, IL-33 and BAFF, help to shape the local accumulation and activation of Th2 responses and B cell immunoglobulin production. Epithelial cells are also downstream targets of molecules that activate IL-13R and EGFR and are responsible for mucus production in both protective immune responses and allergic airway inflammatory diseases. Improved understanding of epithelial immune and inflammatory responses will hopefully suggest new strategies for therapeutic intervention.

Figures

Figure 1. Model summarizing the influence of epithelial cells on innate and adaptive immune responses as well as anti-inflammatory processes in the airways

The left part of figure shows the expression profiles of PRRs in the epithelium. TLRs and lactosylceramide recognize pathogens on the cell surface. In contrast, TLR3, NODs and RNA helicases recognized pathogens intracellularly. After activation of PRRs, epithelial cells produce a wide range of molecules which enhance innate and adaptive immune responses, cell recruitment and mediate anti-inflammatory responses.

Figure 2. Schematic of recently identified pathways of airway inflammation and goblet cell differentiation in epithelial cells

1. EGFR signaling induces the activation of PI3K/Akt to inhibit ciliated cell and Clara cell apoptosis. 2. EGFR signaling and IL-13 signaling regulate goblet cell differentiation. 3. IL-13 signaling induces adipocyte fatty acid-binding protein aP2 that regulates allergic inflammation. 4. IL-13 signaling induces periostin which can bind to the extracellular matrix proteins to induce fibrosis.