Lung Th17 inflammatory responses augment polymeric immunoglobulin receptor expression by the airway epithelium and promote B cell recruitment and increase in secretory IgA levels (39.10)

Abstract

Abstract Polymeric immunoglobulin receptor (pIgR) is a central player in mucosal immunity that mediates delivery of polymeric IgA and IgM to the apical surface via transcytosis across the type I mucosal epithelium. Emerging evidence suggests that Th17 cells, characterized by their production of IL-17, not only mediate autoimmunity but also play key roles in mucosal host defense against extracellular microbes. We demonstrate that adoptive transfer of OVA-specific CD4+ Th17 cells into BALB/c mice, in addition to causing neutrophilic inflammation, mediated a pronounced influx of CD19+ B cells into the lungs following OVA inhalation. Coincident with the cellular recruitment, were the striking elevation in pIgR expression by the airway epithelium and the subsequent increase in IgM and secretory IgA levels. Intranasal administration of IL-17 revealed a key role for this cytokine in the upregulation of pIgR expression by the epithelium. Lung mucosal Th17 responses were markedly regulated by the transfer of antigen-specific CD4+CD25+Foxp3+ regulatory T cells whose suppressive function was restricted to the site of inflammation. These findings support a key role for IL-17-producing Th17 cells in mediating pulmonary immune defense against respiratory pathogens by promoting the expression of pIgR and subsequent transport of mucosal IgA and IgM into the airway lumen.