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Ranjan, Satish; Goihl, Alexander; Kohli, Shrey; Gadi, Ihsan; Pierau, Mandy; Shahzad, Khurrum; Gupta, Dheerendra; Bock, Fabian; Wang, Hongjie; Shaikh, Haroon; Kähne, Thilo; Reinhold, Dirk; Bank, Ute; Zenclussen, Ana C.; Niemz, Jana; Schnöder, Tina M.; Brunner-Weinzierl, Monika; Fischer, Thomas; Kalinski, Thomas; Schraven, Burkhart; Luft, Thomas; Huehn, Jochen; Naumann, Michael; Heidel, Florian H.;

Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells

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  • Medientyp: E-Artikel
  • Titel: Activated protein C protects from GvHD via PAR2/PAR3 signalling in regulatory T-cells
  • Beteiligte: Ranjan, Satish; Goihl, Alexander; Kohli, Shrey; Gadi, Ihsan; Pierau, Mandy; Shahzad, Khurrum; Gupta, Dheerendra; Bock, Fabian; Wang, Hongjie; Shaikh, Haroon; Kähne, Thilo; Reinhold, Dirk; Bank, Ute; Zenclussen, Ana C.; Niemz, Jana; Schnöder, Tina M.; Brunner-Weinzierl, Monika; Fischer, Thomas; Kalinski, Thomas; Schraven, Burkhart; Luft, Thomas; Huehn, Jochen; Naumann, Michael; Heidel, Florian H.;
  • Erschienen: Springer Science and Business Media LLC, 2017
  • Erschienen in: Nature Communications, 8 (2017) 1
  • Sprache: Englisch
  • DOI: 10.1038/s41467-017-00169-4
  • ISSN: 2041-1723
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: AbstractGraft-vs.-host disease (GvHD) is a major complication of allogenic hematopoietic stem-cell(HSC) transplantation. GvHD is associated with loss of endothelial thrombomodulin, but the relevance of this for the adaptive immune response to transplanted HSCs remains unknown. Here we show that the protease-activated protein C (aPC), which is generated by thrombomodulin, ameliorates GvHD aPC restricts allogenic T-cell activation via the protease activated receptor (PAR)2/PAR3 heterodimer on regulatory T-cells (Tregs, CD4+FOXP3+). Preincubation of pan T-cells with aPC prior to transplantation increases the frequency of Tregs and protects from GvHD. Preincubation of human T-cells (HLA-DR4−CD4+) with aPC prior to transplantation into humanized (NSG-AB°DR4) mice ameliorates graft-vs.-host disease. The protective effect of aPC on GvHD does not compromise the graft vs. leukaemia effect in two independent tumor cell models. Ex vivo preincubation of T-cells with aPC, aPC-based therapies, or targeting PAR2/PAR3 on T-cells may provide a safe and effective approach to mitigate GvHD.
  • Zugangsstatus: Freier Zugang