Cellules Dendritiques : biologie et applications cliniques
   

Investigateur Principal : Pr. Régis Josien, MD, PhD,

Inserm, UMR 1064, ITUN, CHU de Nantes

   

The main objective of our project is to better understand some basic biological functions of dendritic cells (DCs) such as antigen presentation, subset specialization and innate functions and to optimize the generation of tolerogenic DCs for the development of clinical applications in transplantation and gene therapy.

DCs play a pivotal role in the control of innate and adaptive immune response. This area of research has been developed in our center during the last 15 years and has led important discoveries (ex: Killer DCs) (Josien et al. J. Exp. Med. 1997) or preclinical applications (ex: tolerogenic DCs in transplantation) (Beriou et al. Curr. Opin. Organ. Transplant. 2012). However, clinical developments in transplantation are rather limited so far as it is necessary to better understand molecular mechanisms of antigen presentation by DCs, DC subset diversity and to better characterize tolerogenic DCs. These steps of basic research are critical for the development of clinical applications.

Specific goals of this project are:

1. To understand the role of the molecule TORID, which has been identified in our laboratory, in antigen cross-presentation by DCs (Condamine et al. J. Leukoc. Biol. 2010).

2. To understand the physiological function of the production of IL-22BP, a soluble and inhibitory receptor for IL-22, by a subset of DCs in the regulation of epithelial homeostasis and inflammatory diseases (Martin et al. Mucosal Immunol. 2013)

3; To optimize the tolerogenic effects of Heme-oxygenase 1 (HO-1) on DCs for the development of clinical applications and to understand the mechanisms of action of HO-1 on the regulation of antigen presentation in vivo (Simon et al. Immunotherapy. 2011)

These projects will require the development of rodent and primate models and the use of existing platform (transgenesis, DTC, recombinant proteins).

Expected results of this projects are to develop new clinical approaches in order to control immune responses in transplantation either using cellular therapy (tolerogenic DCs) or by in vivo targeting of immunomodulatory molecules involved in DC functions (TORID, IL-22BP, HO-1). Moreover, this project will allow reinforcing the DC research area in our center through new international collaborations.