PT  - JOURNAL ARTICLE
AU  - Marijke I. Zonneveld
AU  - Martijn J.C. van Herwijnen
AU  - Marcela M. Fernandez-Gutierrez
AU  - Alberta Giovanazzi
AU  - Anne Marit de Groot
AU  - Marije Kleinjan
AU  - Toni M.M. van Capel
AU  - Alice J.A.M. Sijts
AU  - Leonie S. Taams
AU  - Johan Garssen
AU  - Esther C. de Jong
AU  - Michiel Kleerebezem
AU  - Esther N.M. Nolte-’t Hoen
AU  - Frank A. Redegeld
AU  - Marca H.M. Wauben
TI  - Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses
AID  - 10.1101/2020.04.29.068841
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.04.29.068841
4099  - http://biorxiv.org/content/early/2020/05/01/2020.04.29.068841.short
4100  - http://biorxiv.org/content/early/2020/05/01/2020.04.29.068841.full
AB  - Maternal milk is nature’s first functional food. It plays a crucial role in the development of the infant’s gastrointestinal (GI) tract and the immune system. Extracellular vesicles (EVs) are a heterogeneous population of lipid bilayer enclosed vesicles released by cells for intercellular communication and are a component of milk. Recently, we discovered that human milk EVs contain a unique proteome compared to other milk components. Here, we show that physiological concentrations of milk EVs support epithelial barrier function by increasing cell migration via the p38 MAPK pathway. Additionally, milk EVs inhibit agonist-induced activation of endosomal Toll like receptors TLR3 and TLR9. Furthermore, milk EVs directly inhibit activation of CD4+ T cells by temporarily suppressing T cell activation without inducing tolerance. We show that milk EV proteins target key hotspots of signalling networks that can modulate cellular processes in various cell types of the GI tract.Competing Interest StatementThe authors have declared no competing interest.