title: The SRC family tyrosine kinase HCK and the ETS family transcription factors SPIB and EHF regulate transcytosis across a human follicle-associated epithelium model.
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.
authors: Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California 90095, USA. neaki.asai@ucla.edu
authors: Tsuneaki
authors: T
authors: Asai
authors: Sherie L
authors: SL
authors: Morrison
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051572:Proto-Oncogene Proteins c-hck / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D057900:Transcytosis / Q000276:immunology*
chemical_list: D004268:DNA-Binding Proteins; C403306:EHF protein, human; D007070:Immunoglobulin A; D014157:Transcription Factors; C076877:SPIB protein, human; C496631:HCK protein, human; D051572:Proto-Oncogene Proteins c-hck