Research Group

  • Dr. Jörg Koglin, Principal Investigator
  • Prof. Mary E. Russell, Consultant

Location

  • University of Munich, Munich, Germany

Title

  • Role of Innate Immune Recognition as Initiator of Chronic Rejection after Cardiac Transplantation

Even with optimised immunosuppressive strategies, chronic rejection with the develop­ment of an accelerated form of arteriosclerosis remains the major limitation of long-term graft survival after cardiac transplantation. While acquired immune responses have been identified to propagate this form of rejection, the proximal events leading to their activation remain unknown. Recently, evolutionarily ancient innate immune recognition has been found to control the activation of adaptive immune responses in antibacterial processes. As proximal signalling events, specific molecular patterns are recognised by members of the Toll-like receptor family expressed on antigen-presenting cells.

Activation of the human homologues of this receptor family has been shown to induce the expression of a variety of cytokines and costimulatory molecules known to be crucial for activation of adaptive immune responses in chronic rejection. However, while these innate mecha­nisms are well characterised in the cellular defence against infectious agents, their role in chronic cardiac rejection remains unknown. We hypothesise that innate immune responses play an essential role in the initiation and control of the immune cascade responsible for the chronic rejection of transplanted hearts.

To validate this hypothesis, this project aims to characterise Toll-receptor signalling in monocytes from cardiac trans­plant recipients with and without chronic rejection, to compare costimulatory signalling and cytokine expression in these patients, and to identify potential specific molecular patterns responsible for the activation of innate immunity. Proof of the proposed hypothesis would not only open new ways to stratify the individual risk of transplant recipients to develop cardiac allograft vasculopathy (CAV), but would also point towards novel strategies to interrupt innate immune recognition in order to prevent chronic rejection after cardiac transplantation.