Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Buzas, Edit Iren
MetadataShow full item record
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.
CitationMesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3(+) regulatory T cells. 2017 Eur. J. Immunol.
AffiliationHelmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalEuropean journal of immunology
The following license files are associated with this item:
- Neonatally imprinted stromal cell subsets induce tolerogenic dendritic cells in mesenteric lymph nodes.
- Authors: Pezoldt J, Pasztoi M, Zou M, Wiechers C, Beckstette M, Thierry GR, Vafadarnejad E, Floess S, Arampatzi P, Buettner M, Schweer J, Fleissner D, Vital M, Pieper DH, Basic M, Dersch P, Strowig T, Hornef M, Bleich A, Bode U, Pabst O, Bajénoff M, Saliba AE, Huehn J
- Issue date: 2018 Sep 25
- The intestinal micro-environment imprints stromal cells to promote efficient Treg induction in gut-draining lymph nodes.
- Authors: Cording S, Wahl B, Kulkarni D, Chopra H, Pezoldt J, Buettner M, Dummer A, Hadis U, Heimesaat M, Bereswill S, Falk C, Bode U, Hamann A, Fleissner D, Huehn J, Pabst O
- Issue date: 2014 Mar
- Mesenteric lymph node CD11b<sup>-</sup> CD103<sup>+</sup> PD-L1<sup>High</sup> dendritic cells highly induce regulatory T cells.
- Authors: Shiokawa A, Kotaki R, Takano T, Nakajima-Adachi H, Hachimura S
- Issue date: 2017 Sep
- Crucial roles of B7-H1 and B7-DC expressed on mesenteric lymph node dendritic cells in the generation of antigen-specific CD4+Foxp3+ regulatory T cells in the establishment of oral tolerance.
- Authors: Fukaya T, Takagi H, Sato Y, Sato K, Eizumi K, Taya H, Shin T, Chen L, Dong C, Azuma M, Yagita H, Malissen B, Sato K
- Issue date: 2010 Sep 30
- Rapid and Efficient Generation of Regulatory T Cells to Commensal Antigens in the Periphery.
- Authors: Nutsch K, Chai JN, Ai TL, Russler-Germain E, Feehley T, Nagler CR, Hsieh CS
- Issue date: 2016 Sep 27