Research Group

  • Prof. David Adams, Principal Investigator
  • Dr. Sarah Goddard, Co-Investigator


  • University of Birmingham, Edgbaston, UK


  • Human Hepatic Dendritic Cells Induce Tolerance via Notch Signalling

Although liver transplantation is increasingly successful, patients need to take powerful drugs for the rest of their lives to prevent rejection. These drugs have serious side-effects and quality of life would be greatly enhanced if their use could be avoided or minimised. One way to do this would be to develop a treatment that allowed the transplant to be accepted by the patient without the need for long-term anti-rejection drugs, a phenomenon called immunological tolerance. There is evidence that the liver may be more amenable to such treatment than other organs because in some animals livers can be transplanted without any anti-rejection drugs and in humans liver transplants require less anti-rejection therapy than heart or kidney transplants. The underlying mechanisms of this tolerance are not understood.

We shall investigate the role of important regulatory cells - dendritic cells (DCs) - in this process. DCs have unique properties that allow them to regulate immune responses by switching on or off lymphocytes, the cells that cause transplant rejection. We have shown that DCs from human liver differ when compared with those from other sites, such as the skin (skin transplants are rapidly rejected). We now want to find out whether these differences allow the liver DCs to switch off rejection and, if so, how they do this.

We have found that human liver DCs express much greater amounts of a molecule called Jagged when compared with skin DCs. Jagged binds to a receptor called Notch on other cells and this interaction can affect the fate of the cell and prevent it from becoming activated. Because Notch is present on lymphocytes, we propose that Jagged on liver DCs will be able to trigger notch and turn the potentially harmful lymphocytes into regulatory cells that prevent rejection from developing. If this new hypothesis is correct, it may be possible to manipulate the Jagged/Notch system to increase the chance of transplants being accepted without the need for anti-rejection drugs.