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

Maria Pasztoi, Joern Pezoldt, Michael Beckstette, Christoph Lipps, Dagmar Wirth, Manfred Rohde, Krisztina Paloczi, E. Búzás, Jochen Huehn

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2142-2152
Number of pages11
JournalEuropean Journal of Immunology
Volume47
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

Fingerprint

Regulatory T-Lymphocytes
Stromal Cells
Lymph Nodes
Cell Line
Peripheral Tolerance
Foster Home Care
Extracellular Vesicles
RNA
Phenotype
Antigens
Food
Skin

Keywords

  • Extracellular vesicles
  • Fibroblastic reticular cells
  • Intestinal tolerance
  • Mesenteric lymph nodes
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells. / Pasztoi, Maria; Pezoldt, Joern; Beckstette, Michael; Lipps, Christoph; Wirth, Dagmar; Rohde, Manfred; Paloczi, Krisztina; Búzás, E.; Huehn, Jochen.

In: European Journal of Immunology, Vol. 47, No. 12, 01.12.2017, p. 2142-2152.

Research output: Contribution to journalArticle

Pasztoi, Maria ; Pezoldt, Joern ; Beckstette, Michael ; Lipps, Christoph ; Wirth, Dagmar ; Rohde, Manfred ; Paloczi, Krisztina ; Búzás, E. ; Huehn, Jochen. / Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3+ regulatory T cells. In: European Journal of Immunology. 2017 ; Vol. 47, No. 12. pp. 2142-2152.
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