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J Biol Chem. 2013 Apr 12;288(15):10395-405. doi: 10.1074/jbc.M112.437475. Epub 2013 Feb 25.

The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model.

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  • 1Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California 90095, USA. neaki.asai@ucla.edu

Abstract

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.

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