Role of IL-13 and TGF-beta1 in the development of chronic rejection in solid organ transplantation

• Applicant: Professor Dr. Stefan Fichtner-Feigl
• Subject Area: General and Visceral Surgery
• Term: from 2010 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 160225957

• Final Report Year: 2018

Final Report Abstract

In summary, we were able to add value information to the molecular events being responsible for chronic allograft rejection and fibrotoc organ remodelling. TGF-β1 mediated downstream pro-fibrotic pathways are regulated by early innate immune activation. Inhibition of the innate immune system in the early phase after transplantation leads to beneficial long-term effects and prevents fibrotic allograft remodelling. This set of new information can be used therapeutically by targeting innate immune cells via antibody blockade. Translational studies need to follow to exploit this potential.

Publications

• (2011) Interleukin-33 prolongs allograft survival during chronic cardiac rejection. Transpl Int. 24(10):1027-1039
  Brunner SM, Schiechl G, Falk W, Schlitt HJ, Geissler EK, Fichtner-Feigl S
  (See online at https://doi.org/10.1111/j.1432-2277.2011.01306.x)
• (2012) Biliodigestive anastomosis: indications, complications and interdisciplinary management. Chirurg. 2012 Dec;83(12):1097-1098
  Goessmann H, Lang SA, Fichtner-Feigl S, Scherer MN, Schlitt HJ, Stroszczynski C, Schreyer AG, Schnitzbauer AA
  (See online at https://doi.org/10.1007/s00104-012-2365-z)
• (2013) Bile duct damage after cold storage of deceased donor livers predicts biliary complications after liver transplantation. J Hepatol. 58(6):1133-1139
  Brunner SM, Junger HH, Ruemmele P, Schnitzbauer AA, Doenecke A, Kirchner GI, Farkas SA, Loss M, Scherer MN, Schlitt HJ, Fichtner-Feigl S
  (See online at https://doi.org/10.1016/j.jhep.2012.12.022)
• (2013) IL-13 signaling via IL-13Rα2 triggers TGF-β1-dependent allograft fibrosis.Transplant Res. 22;2(1):16
  Brunner SM, Schiechl G, Kesselring R, Martin M, Balam S, Schlitt HJ, Geissler EK, Fichtner-Feigl S
  (See online at https://doi.org/10.1186/2047-1440-2-16)
• (2013) Inhibition of innate co-receptor TREM-1 signaling reduces CD4(+) T cell activation and prolongs cardiac allograft survival. Am J Transplant. 13(5):1168-1180
  Schiechl G, Brunner SM, Kesselring R, Martin M, Ruemmele P, Mack M, Hirt SW, Schlitt HJ, Geissler EK, Fichtner-Feigl S
  (See online at https://doi.org/10.1111/ajt.12186)
• (2014) IL-13 orchestrates resolution of chronic intestinal inflammation via phosphorylation of glycogen synthase kinase-3β. J Immunol. 192(8):3969-3980
  Fichtner-Feigl S, Kesselring R, Martin M, Obermeier F, Ruemmele P, Kitani A, Brunner SM, Haimerl M, Geissler EK, Strober W, Schlitt HJ
  (See online at https://doi.org/10.4049/jimmunol.1301072)
• (2016) Basophils trigger fibroblast activation in cardiac allograft fibrosis development. Am J Transplant. 16(9):2574-2588
  Schiechl G, Hermann FJ, Rodriguez Gomez M, Kutzi S, Schmidbauer K, Talke Y, Neumayer S, Goebel N, Renner K, Brühl H, Karasuyama H, Obata-Ninomiya K, Utpatel K, Evert M, Hirt SW, Geissler EK, Fichtner-Feigl S, Mack M
  (See online at https://doi.org/10.1111/ajt.13764)
• (2017) Bile duct regeneration and immune response by passenger lymphocytes signals biliary recovery versus complications after liver transplantation. Liver Transpl. 23(11):1422-1432
  Junger HH, Schlitt HJ, Geissler EK, Fichtner-Feigl S, Brunner SM
  (See online at https://doi.org/10.1002/lt.24836)