Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621113
Title:
Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells.
Authors:
Pasztoi, Maria; Pezoldt, Joern; Beckstette, Michael; Lipps, Christoph; Wirth, Dagmar; Rohde, Manfred ( 0000-0003-0522-3580 ) ; Paloczi, Krisztina; Buzas, Edit Iren; Huehn, Jochen ( 0000-0001-8071-1379 )
Abstract:
Intestinal regulatory T cells (Tregs) are fundamental in peripheral tolerance toward commensals and food-borne antigens. Accordingly, gut-draining mesenteric lymph nodes (mLNs) represent a site of efficient peripheral de novo Treg induction when compared to skin-draining peripheral LNs (pLNs), and we had recently shown that LN stromal cells substantially contribute to this process. Here, we aimed to unravel the underlying molecular mechanisms and generated immortalized fibroblastic reticular cell lines (iFRCs) from mLNs and pLNs, allowing unlimited investigation of this rare stromal cell subset. In line with our previous findings, mLN-iFRCs showed a higher Treg-inducing capacity when compared to pLN-iFRCs. RNA-seq analysis focusing on secreted molecules revealed a more tolerogenic phenotype of mLN- as compared to pLN-iFRCs. Remarkably, mLN-iFRCs produced substantial numbers of microvesicles (MVs) that carried elevated levels of TGF-β when compared to pLN-iFRC-derived MVs, and these novel players of intercellular communication were shown to be responsible for the tolerogenic properties of mLN-iFRCs. Thus, stromal cells originating from mLNs contribute to peripheral tolerance by fostering de novo Treg induction using TGF-β-carrying MVs. This finding provides novel insights into the subcellular/molecular mechanisms of de novo Treg induction and might serve as promising tool for future therapeutic applications to treat inflammatory disorders.
Affiliation:
Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells. 2017 Eur. J. Immunol.
Journal:
European journal of immunology
Issue Date:
18-Aug-2017
URI:
http://hdl.handle.net/10033/621113
DOI:
10.1002/eji.201746960
PubMed ID:
28833065
Type:
Article
Language:
en
ISSN:
1521-4141
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM); publications of the central unit for microscopy (ZEIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorPasztoi, Mariaen
dc.contributor.authorPezoldt, Joernen
dc.contributor.authorBeckstette, Michaelen
dc.contributor.authorLipps, Christophen
dc.contributor.authorWirth, Dagmaren
dc.contributor.authorRohde, Manfreden
dc.contributor.authorPaloczi, Krisztinaen
dc.contributor.authorBuzas, Edit Irenen
dc.contributor.authorHuehn, Jochenen
dc.date.accessioned2017-09-19T13:06:36Z-
dc.date.available2017-09-19T13:06:36Z-
dc.date.issued2017-08-18-
dc.identifier.citationMesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells. 2017 Eur. J. Immunol.en
dc.identifier.issn1521-4141-
dc.identifier.pmid28833065-
dc.identifier.doi10.1002/eji.201746960-
dc.identifier.urihttp://hdl.handle.net/10033/621113-
dc.description.abstractIntestinal regulatory T cells (Tregs) are fundamental in peripheral tolerance toward commensals and food-borne antigens. Accordingly, gut-draining mesenteric lymph nodes (mLNs) represent a site of efficient peripheral de novo Treg induction when compared to skin-draining peripheral LNs (pLNs), and we had recently shown that LN stromal cells substantially contribute to this process. Here, we aimed to unravel the underlying molecular mechanisms and generated immortalized fibroblastic reticular cell lines (iFRCs) from mLNs and pLNs, allowing unlimited investigation of this rare stromal cell subset. In line with our previous findings, mLN-iFRCs showed a higher Treg-inducing capacity when compared to pLN-iFRCs. RNA-seq analysis focusing on secreted molecules revealed a more tolerogenic phenotype of mLN- as compared to pLN-iFRCs. Remarkably, mLN-iFRCs produced substantial numbers of microvesicles (MVs) that carried elevated levels of TGF-β when compared to pLN-iFRC-derived MVs, and these novel players of intercellular communication were shown to be responsible for the tolerogenic properties of mLN-iFRCs. Thus, stromal cells originating from mLNs contribute to peripheral tolerance by fostering de novo Treg induction using TGF-β-carrying MVs. This finding provides novel insights into the subcellular/molecular mechanisms of de novo Treg induction and might serve as promising tool for future therapeutic applications to treat inflammatory disorders.en
dc.language.isoenen
dc.relationinfo:eu-repo/grantAgreement/EC/H2020/656319en
dc.rightsopenAccessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleMesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalEuropean journal of immunologyen

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