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Therapeutic targeting in transplantation

Dr. Jurij Kiefer

Dr. Verena K. Horner

Laura Schneider

The innate immune system as a therapeutic target in transplantation

Vascularized composite allotransplantation (VCA) implicates the transfer of multiple types of tissue from one individual to another as a functional unit, such as hand or face transplantation. Emerged from developments in microsurgical techniques and solid organ transplantation, VCA can achieve improved functional and cosmetic outcome not possible with autologous free tissue transfer. In contrast to conventional organ transplantation, however, one is faced with the ethical issue that VCA is a quality of life-enhancing reconstruction rather than a life-saving intervention.

Improvements in allograft survival over the last decades can be attributed to the development of potent inhibitors of T-cell activation and proliferation. Despite these advances, a substantial proportion of transplanted organs is still rejected. Immune response to allogeneic tissue is a highly coordinated event that takes place in complex and specialised tissue microenvironments. An integrated view of innate and adaptive immune response to transplanted tissue requires a better understanding of how immune cells communicate and fulfil their task in vivo.

 

Two-photon microscopy of muscle microcirculation in a VCA model. GFP-labeled monocytes (green) are adherent to the vessel walls.

 

A key cell that participates in T-cell activation is the dendritic cell, but it is unclear how the maturation of these cells is induced to initiate the immune response eventually. Recently it has been shown that innate recognition of allogeneic non-self by monocytes can initiate graft rejection after transplantation. We use sophisticated intra-vital imaging strategies that will allow us to identify how the innate immune system contributes to non-self recognition and priming of dendritic cells. Our aim is to therapeutically target the innate immune response to reduce allograft rejection and make VCA a safe and feasible option in reconstructive microsurgery.  

 

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