Interleukin (IL)-17 is produced by several cell subtypes including T helper (Th)17 lymphocytes, CD8+ T cells, gamma-deltaT cells, NK/NKT cells and neutrophils. Th17 cells specifically express the transcription factor RORgamma-t and IL-17 production is associated with tissue neutrophilic infiltration. We recently made the surprising observation that alloreactive Th17 cell expansion is uncontrolled or even favored by natural regulatory T cells. In parallel, we found that IL-4-deficient mice reject MHC-class II disparate skin allografts through a neutrophil-dependent mechanism, suggesting a role for IL-17 in this process. Therefore, Th17 immunity might represent an alternate pathway of allograft rejection and a barrier to tolerance induction strategies based on regulatory T cells. The aim of this project is to explore in murine models the conditions under which IL-17-producing cells mediate acute or chronic rejection of allografts, to compare the susceptibility of different grafted tissues (skin, lung, heart) to IL-17-mediated damage, and to explore strategies to inhibit Th17-mediated rejection.

Principal investigator: Alain LEMOINE (MD-PhD)
Associate investigator: Michel BRAUN (PhD)
Post-doctoral fellow: Louis-Marie CHARBONNIER
MD-PhD students: Benoît VOKAER, Philippe LEMAITRE
Technical assistant: Carole KUBJAK

Benghiat FS, Charbonnier LM, Vokaer B, De Wilde V, Le Moine A. Interleukin 17-producing T helper cells in alloimmunity. Transplant Rev 2009; 23: 11-18

Benghiat FS, Craciun L, De Wilde V, Dernies T, Kubjak C, Lhomme F, Goldman M, Le Moine A. IL-17 production elicited by allo-MHC class II recognition depends on CD25posCD4pos T cells. Transplantation 2008; 85: 943-949

Benghiat S, Graca L, Braun MY, Detienne S, Moore F, Buonocore S, Waldmann H, Goldman M, Le Moine A. Critical influence of natural regulatory CD25⁺ T cells on the fate of allografts in absence of immunosuppression. Transplantation 2005; 79 : 648-654.

Government of the Walloon Region
GSK Biologicals
The Fund for Scientific Research (F.R.S - FNRS) and the Télévie Programme
The Belgian Science Policy
The European Commission
The Erasme Fund The Wiener-Anspach Foundation
The Belgian Kid's Fund
The Roche Organ Transplantation Research Foundation
The Dimitris and Noela Nakos Foundation
Roche Pharmaceuticals, Belgium
Wittycell S.A.S