Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses

Marijke I. Zonneveld, Martijn J.C. van Herwijnen, Marcela M. Fernandez-Gutierrez, Alberta Giovanazzi, Anne Marit de Groot, Marije Kleinjan, Toni M.M. van Capel, Alice J.A.M. Sijts, Leonie S. Taams, Johan Garssen, Esther C. de Jong, Michiel Kleerebezem, Esther N.M. Nolte-’t Hoen, Frank A. Redegeld, Marca H.M. Wauben*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Article numbere12071
JournalJournal of Extracellular Vesicles
Volume10
Issue number5
DOIs
Publication statusE-pub ahead of print - 10 Mar 2021

Keywords

  • breast milk
  • exosomes
  • extracellular vesicles
  • gastrointestinal tract
  • human milk
  • immune modulation
  • immune system development
  • oral cavity
  • T cell modulation
  • TLR modulation

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