Abstract
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.
Highlights
We show that cell surface levels of E-cadherin and EPCAM were significantly decreased in the presence of milk Extracellular vesicles (EVs) (Figure 2h-i and Supplementary Figure 3), which would allow for faster movement of the epithelial cells
We demonstrate that human milk EVs directly enhance gingival epithelial cell migration via p38 MAPK and cytoskeletal remodelling
It has previously been shown that EVs from other sources can stimulate TLR2 (Bretz et al, 2013), TLR3 (Seo et al, 2016), TLR4 (Bretz et al, 2013) and TLR9 (Ye et al, 2017), we show that milk EVs do not activate TLR3 and TLR9
Summary
H and i) Epithelial Ca9-22 cells were cultured for 5 h in medium or together with milk EVs or EV-depleted control after which cell surface expression of E-cadherin (h) or EPCAM was determined (i). I) Western blot analysis for the presence of TLR3 on whole cell lysate of Ca9-22 cells cultured in medium alone or stimulated with poly I:C with or without milk EVs or EV-depleted control.
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