Dendritic cells and immunoregulation in transplantation and immunopathology
Régis Josien
Team Leader

Professor

Dendritic cells (DCs) play a central role in the control of adaptive and innate immunity. RJ research mainly focuses on the functional specializations and the role of DC subsets in normal immune responses and immune-mediated inflammatory diseases (IMIDs) with an emphasis on their role in innate immunity and immunoregulation.

Description

Dendritic cells (DCs) play a central role in the control of immune responses through their unique ability not only to initiate adaptive immunity but also to promote and maintain T cell tolerance. In addition, DCs exhibit innate functions such as cytokine secretion, cytotoxicity and control of innate cell functions. DCs are actually a heterogenous population made of several subsets endowed with specific functions.

RJ research mainly focuses on the function and the role of DC subsets in normal immune responses and immune-mediated inflammatory diseases (IMIDs) with an emphasis on their role in innate immunity and immunoregulation. Major current projects are:

Role of DC-derived IL-22 binding protein (IL-22BP) in the control of the function of IL-22 during inflammation and steady state

IL-22 is a cytokine produced by various immune cells and acting on epithelial cells by promoting anti-microbial responses and protection. As such, IL-22 plays a central role in mucosal immunity. IL-22BP is a soluble inhibitory receptor of IL-22. We have shown that the main source of IL-22BP is a subset of conventional DCs (Mucosal Immunol. 2014) in mucosal and lymphoid tissues. Using IL-22BP KO rats we generated in the lab, we showed that DC-derived IL-22BP played an important role in the control of protective actions of IL-22 during experimental colitis (Mucosal Immunol 2016). On the other hand, we showed that IL-22BP deficiency worsened skin inflammation in psoriasis like model in rodents (J Immunol 2017). We currently investigate the role of IL-22BP in inflammatory bowel diseases (IBDs) in human and in gut homeostasis in rodents.

Role of DC subsets in ANCA-associated vasculitis

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) are chronic and systemic autoimmune diseases characterized by small vessels inflammation and necrosis that can involve many organs and tissues. ANCA are pathogenic auto-antibodies but mechanisms leading to autoimmune response induction and maintenance in AAV are poorly understood. The aim of this project is to better understand the role of innate immunity and DC subsets in the pathogenesis of AAV. We have previously shown that both mDCs and pDCs are reduced in the blood of AAV patients (PlosONE 2011), and that mDCs exhibited a dysregulated response to TLR stimulation (Frontiers Immunol 2017). AAV are also characterized by a dramatic and persistent reduction of circulating mucosal-associated invariant T (MAIT) cells (J Autoimmun 2016).