- Dr. Ignacio Anegon, Principal Investigator
- Dr. Christine Chaveau, Post-doctoral Fellow
- Dr. Severine Remy, Technician
- Mr. Régis Brion, Technician
- Mr. Laurent Tesson, Technician
- Dr. Marc Gregoire, Research Associate
- Dr. Maria Grazia Roncarolo, Research Associate
- Dr. Katja Kotsh, Research Associate
- Dr. Georges Kollias, Research Associate
- INSERM U643, ITERT, Nantes, France
- Heme Oxygenase-1 promotes Tolerogenic Dendritic Cells: Analysis of Mechanisms and in vivo Applications
Despite enormous progress in controlling acute rejection and prolonging graft survival, continuous immunosuppression after transplantation is associated with side effects such as opportunistic infections and cancer, as well as progressive graft failure due to chronic rejection. The attainment of specific inhibition of immune responses directed against the donor antigens while preserving immune responses against infectious agents or cancer cells (i.e. tolerance) would allow for a reduction or elimination of immunosuppressive drug treatment.
Heme oxygenase-1 (HO-1) is an enzyme that has anti-inflammatory and graft protective actions. Dendritic cells (DCs) are not only initiators of pro-inflammatory but also of tolerogenic immune responses. It has recently been shown that HO-1 inhibits the pro-inflammatory properties of DCs while promoting their tolerogenic potential.
This project aims to more precisely define the mechanisms by which HO-1 promotes the tolerogenic potential of DCs. Particular attention will be paid to the effects of HO-1 on the capacity of DCs to generate different subpopulations of T lymphocytes with tolerogenic activities. The intracellular signaling pathways as well as the production of extracellular mediators of DC activity will also be analysed. DCs expressing HO-1 will be used to induce tolerance in rodent models of organ transplantation.
Such basic knowledge of the mechanisms whereby HO-1 acts on DCs and the use of HO-1-overexpressing DCs in transplantation may make it possible in the future to induce donor-specific tolerance and thus have a major impact on transplantation.