The SRC Family Tyrosine Kinase HCK and the ETS Family Transcription Factors SPIB and EHF Regulate Transcytosis across a Human Follicle-associated Epithelium Model

A critical step in the induction of adaptive mucosal immunity is antigen transcytosis, in which luminal antigens are transported to organized lymphoid tissues across the follicle-associated epithelium (FAE) of Peyer's patches. However, virtually nothing is known about intracellular signaling proteins and transcription factors that regulate apical-to-basolateral transcytosis. The FAE can transcytose a variety of luminal contents, including inert particles, in the absence of specific opsonins. Furthermore, it expresses receptors for secretory immunoglobulin A(SIgA), the main antibody in mucosal secretions, and uses them to efficiently transcytose SIgA-opsonized particles present in the lumen. Using a human FAE model, we show that the tyrosine kinase HCK regulates apical-to-basolateral transcytosis of non-opsonized and SIgA-opsonized particles. We also show that, in cultured intestinal epithelial cells, ectopic expression of the transcription factor SPIB or EHF is sufficient to activate HCK-dependent apical-to-basolateral transcytosis of these particles. Our results provide the first molecular insights into the intracellular regulation of antigen sampling at mucosal surfaces.