Respiratory Tract Epithelial Cells Express Retinaldehyde Dehydrogenase ALDH1A and Enhance IgA Production by Stimulated B Cells in the Presence of Vitamin A

Morbidity and mortality due to viral infections are major health concerns, particularly when individuals are vitamin A deficient. Vitamin A deficiency significantly impairs mucosal IgA, a first line of defense against virus at its point of entry. Previous reports have suggested that CD11c(Hi) dendritic cells (DCs) of the gastrointestinal tract produce retinaldehyde dehydrogenase (ALDH1A), which metabolizes vitamin A precursors to retinoic acid to support normal mucosal immunity. Given that the upper respiratory tract (URT) and gastrointestinal tract share numerous characteristics, we asked if the CD11c(Hi) DCs of the URT might also express ALDH1A. To address this question, we examined both CD11c(Hi) test cells and CD11c(Lo/neg) control cells from nasal tissue. Surprisingly, the CD11c(Lo/neg) cells expressed more ALDH1A mRNA per cell than did the CD11c(Hi) cells. Further evaluation of CD11c(Lo/neg) populations by PCR and staining of respiratory tract sections revealed that epithelial cells were robust producers of both ALDH1A mRNA and protein. Moreover, CD11c(Lo/neg) cells from nasal tissue (and a homogeneous respiratory tract epithelial cell line) enhanced IgA production by lipopolysaccharide (LPS)-stimulated splenocyte cultures in the presence of the retinoic acid precursor retinol. Within co-cultures, there was increased expression of MCP-1, IL-6, and GM-CSF, the latter two of which were necessary for IgA upregulation. All three cytokines/chemokines were expressed by the LPS-stimulated respiratory tract epithelial cell line in the absence of splenocytes. These data demonstrate the autonomous potential of respiratory tract epithelial cells to support vitamin A-mediated IgA production, and encourage the clinical testing of intranasal vitamin A supplements in vitamin A deficient populations to improve mucosal immune responses toward respiratory tract pathogens and vaccines.