Research Group

  • Dr. Régis Josien, Principal Investigator
  • Dr. Maria-Cristina Cuturi, Co-Investigator
  • Dr. Ignacio Anegon, Research Associate
  • Cédric Lovet, Research Associate
  • Cécile Voisine, Research Associate
  • Jean-Marie Heslan, Research Associate
  • Dr. Yongwon Choi, Consultant


  • INSERM, Nantes, France


  • The Role of TRANCE/RANK Interaction during Allogenic Immune Responses

Understanding immune mechanisms that lead to acute and chronic allograft rejection is an important step towards identification of molecular targets of current and new immunosuppressive drugs. Recent results have shown that the CD40L molecule, which is expressed on activated T cells, and its counter receptor CD40, expressed on antigen-presenting cells (dendritic cells, macrophages and B lymphocytes), represent a major pathway for T cell activation. CD40L blockade has been shown to delay allograft rejection in rodents and monkeys and will probably be used in the future in human organ transplantation.

Recently, a new member of the tumour necrosis factor (TNF) family, called TRANCE (TNF-related activation-induced cytokine) has been described. This molecule shares functional properties with CD40L but appears to be more specialised in the interaction between T cells and dendritic cells, two subsets that play a pivotal role in immune responses to allografts. In vivo studies indicate that, in the absence of the CD40L pathway, the immune system can use the TRANCE pathway to activate T helper cells.

In this proposal, we will analyse the role of TRANCE/RANK interactions during immune responses leading to acute and chronic allograft rejection using rat models. The expression of TRANCE and its receptor RANK will be assessed in allografts and lymphoid organs in different experimental settings. TRANCE blocking reagents will be injected into allograft recipients to determine the role of this pathway in experimental acute and chronic allograft rejection. The manipulation of this system will include gene transfer experiments using recombinant adenoviruses. We will also analyse immune responses to allografts in TRANCE-deficient mice. Based on these studies and their results, we will design new experiments to test the effects of TRANCE blockade in a primate model of renal allograft.