TY - UNPB
T1 - Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses
AU - Zonneveld, M.I.
AU - van Herwijnen, M.J.C.
AU - Fernandez-Gutierrez, Marcela
AU - Giovanazzi, A.
AU - de Groot, A.M.
AU - Kleinjan, M.
AU - van Capel, T.M.
AU - Sijts, E.J.A.M.
AU - Taams, L.S.
AU - Garssen, J.
AU - de Jong, E.
AU - Kleerebezem, Michiel
AU - t Hoen, E.N.M.
AU - Redegeld, F.A.M.
AU - Wauben, M.H.M.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
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.
U2 - 10.1101/2020.04.29.068841
DO - 10.1101/2020.04.29.068841
M3 - Preprint
T3 - bioRxiv
BT - Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses
ER -