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Unravelling the Role of Trophoblastic-Derived Extracellular Vesicles in Regulatory T Cell Differentiation

Department of Genetics, Cell- and Immunobiology, Semmelweis University, H-1085 Budapest, Hungary
MS Proteomics Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, H-1051 Budapest, Hungary
MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, H-1085 Budapest, Hungary
HCEMM-SE Extracellular Vesicle Research Group, H-1085 Budapest, Hungary
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3457;
Received: 21 June 2019 / Revised: 9 July 2019 / Accepted: 11 July 2019 / Published: 14 July 2019
(This article belongs to the Special Issue Extracellular Vesicles and Metastatic Niche)
PDF [1920 KB, uploaded 14 July 2019]


Regulatory T cells (Treg) are mandatory elements in the maintenance of human pregnancy, but their de novo differentiation has not been completely exposed. HSPE1 chaperone expressing trophoblast cells may have a role in it. Trophoblast-derived extracellular vesicles (EVs), either at the feto–maternal interface or in circulation, target CD4+ T cells. We hypothesized that HSPE1-associated trophoblastic cell line (BeWo)-derived EVs are active mediators of Treg cell differentiation. We proved at first that recombinant HSPE1 promote human Treg cell differentiation in vitro. Developing a CRISPR-Cas9 based HSPE1 knockout BeWo cell line we could also demonstrate, that EV-associated HSPE1 induces Treg development. Next-generation sequencing of miRNA cargo of BeWo-EVs characterized the regulatory processes of Treg polarization. By the use of single-cell transcriptomics analysis, seven Treg cell subtypes were distinguished and we demonstrated for the first time that the expression level of HSPE1 was Treg subtype dependent, and CAPG expression is characteristic to memory phenotype of T cells. Our data indicate that HSPE1 and CAPG may be used as markers for identification of Treg subtypes. Our results suggest, that trophoblastic-derived iEVs-associated HSPE1 and miRNA cargo have an important role in Treg cell expansion in vitro and HSPE1 is a useful marker of Treg subtype characterization. View Full-Text
Keywords: extracellular vesicles; EVs; HSPE1; miRNA; C19MC; regulatory T cells extracellular vesicles; EVs; HSPE1; miRNA; C19MC; regulatory T cells

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Kovács, Á.F.; Fekete, N.; Turiák, L.; Ács, A.; Kőhidai, L.; Buzás, E.I.; Pállinger, É. Unravelling the Role of Trophoblastic-Derived Extracellular Vesicles in Regulatory T Cell Differentiation. Int. J. Mol. Sci. 2019, 20, 3457.

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