TY - JOUR
T1 - Human milk extracellular vesicles target nodes in interconnected signalling pathways that enhance oral epithelial barrier function and dampen immune responses
AU - Zonneveld, Marijke I.
AU - van Herwijnen, Martijn J. C.
AU - Fernandez-Gutierrez, Marcela M.
AU - Giovanazzi, Alberta
AU - de Groot, Anne Marit
AU - Kleinjan, Marije
AU - van Capel, Toni M. M.
AU - Sijts, Alice J. A. M.
AU - Taams, Leonie S.
AU - Garssen, Johan
AU - de Jong, Esther C.
AU - Kleerebezem, Michiel
AU - Nolte-’t Hoen, Esther N. M.
AU - Redegeld, Frank A.
AU - Wauben, Marca H. M.
N1 - Funding Information: This work was supported by project 11676 within the framework of a partnership program jointly funded by Nutricia Research and the Dutch Technology Foundation STW, which is part of the Netherlands Organization for Scientific Research (NWO), and is partly funded by the Ministry of Economic Affairs (to Marijke I. Zonneveld; Martijn J.C. van Herwijnen; Frank A. Redegeld; Esther N.M. Nolte‐’t Hoen; Marca H.M. Wauben). The European Union's Horizon 2020 Framework Programme under the grant FETOPEN‐801367 evFOUNDRY (to Martijn J.C. van Herwijnen; Marije Kleinjan; Marca H.M. Wauben). The European Union's Horizon 2020 research and innovation Programme under the grant Marie Skłodowska‐Curie‐722148 TRAIN‐EV (to Alberta Giovanazzi; Marca H.M. Wauben). The TiFN Food and Nutrition; project OH001, ‘novel strategies to promote oral health’ (to Marcela M. Fernandez‐Gutierrez; Michiel Kleerebezem). The European Research Council under the 441 European Union's Seventh Framework Programme (FP/2007‐2013)/ERC Grant Agreement number 442 337581 (to Esther N.M. Nolte‐’t Hoen). The authors are grateful to Bart van der Hee (Host‐Microbe Interactomics Group, Wageningen University) for his help with the single‐cell tracking analysis of the re‐epithelialization image series and Chris A.H. van de Lest for discussions and help on statistical analysis. Publisher Copyright: © 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles
PY - 2021/3/1
Y1 - 2021/3/1
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.
KW - T cell modulation
KW - TLR modulation
KW - breast milk
KW - exosomes
KW - extracellular vesicles
KW - gastrointestinal tract
KW - human milk
KW - immune modulation
KW - immune system development
KW - oral cavity
UR - http://www.scopus.com/inward/record.url?scp=85102952940&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jev2.12071
DO - https://doi.org/10.1002/jev2.12071
M3 - Article
C2 - 33732416
SN - 2001-3078
VL - 10
JO - Journal of extracellular vesicles
JF - Journal of extracellular vesicles
IS - 5
M1 - e12071
ER -