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

Pasztoi M, Pezoldt J, Beckstette M, Lipps C, Wirth D, Rohde M, Paloczi K, Buzas EI, Huehn J (2017)
European Journal of Immunology 47(12): 2142-2152.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Pasztoi, Maria; Pezoldt, Joern; Beckstette, MichaelUniBi; Lipps, Christoph; Wirth, Dagmar; Rohde, Manfred; Paloczi, Krisztina; Buzas, Edit Iren; Huehn, Jochen
Abstract / Bemerkung
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.
Erscheinungsjahr
2017
Zeitschriftentitel
European Journal of Immunology
Band
47
Ausgabe
12
Seite(n)
2142-2152
ISSN
00142980
Page URI
https://pub.uni-bielefeld.de/record/2953296

Zitieren

Pasztoi M, Pezoldt J, Beckstette M, et al. Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells. European Journal of Immunology. 2017;47(12):2142-2152.
Pasztoi, M., Pezoldt, J., Beckstette, M., Lipps, C., Wirth, D., Rohde, M., Paloczi, K., et al. (2017). Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells. European Journal of Immunology, 47(12), 2142-2152. https://doi.org/10.1002/eji.201746960
Pasztoi, M., Pezoldt, J., Beckstette, M., Lipps, C., Wirth, D., Rohde, M., Paloczi, K., Buzas, E. I., and Huehn, J. (2017). Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells. European Journal of Immunology 47, 2142-2152.
Pasztoi, M., et al., 2017. Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells. European Journal of Immunology, 47(12), p 2142-2152.
M. Pasztoi, et al., “Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells”, European Journal of Immunology, vol. 47, 2017, pp. 2142-2152.
Pasztoi, M., Pezoldt, J., Beckstette, M., Lipps, C., Wirth, D., Rohde, M., Paloczi, K., Buzas, E.I., Huehn, J.: Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells. European Journal of Immunology. 47, 2142-2152 (2017).
Pasztoi, Maria, Pezoldt, Joern, Beckstette, Michael, Lipps, Christoph, Wirth, Dagmar, Rohde, Manfred, Paloczi, Krisztina, Buzas, Edit Iren, and Huehn, Jochen. “Mesenteric lymph node stromal cell-derived extracellular vesicles contribute to peripheral de novo induction of Foxp3 regulatory T cells”. European Journal of Immunology 47.12 (2017): 2142-2152.

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