Equipe : Inflammation chronique et système immunitaire
Responsables : Gilles CHIOCCHIA - Maxime BREBAN
Victoire de la médecine The group (Inflamex) is laureate of the prestigious "Victoires de la médecine". (November 2011)
ANR "Chair of Excellence" Grant
The Giraud lab received the Grant "Chair of Excellence"
from the French government. (Jul 2011)
The group in association with two partners has been granted with the highly competitive label "Laboratory of excellence" in the field of Inflammation by the French gouvemment. (May 11)
research offers a unique opportunity in arthritic diseases to link
inflammation and immune system based on a multidisciplinary approach
which involves a two-way process going back and forth between the
analysis of the genetic data, the dissection of immunological mechanisms
and the potential transfer of the findings to the patient management.
Three main pillars constitute the organisation of the research program within the team: 1) Genomic analysis of the diseases with diagnostic and therapeutic applications, 2) Functional validation of targets, and 3) Animal models of the studied diseases.
Chronic inflammatory diseases (CID) result from perturbations of effector cells and soluble mediators of the immune system, on the one hand, and local target tissue abnormalities, on the other. The precise mechanisms leading to inflammation during the course of these diseases are still incompletely understood and the available treatments inadequate. The aim of our team is to increase understanding of mechanisms of chronic inflammation, by focusing mainly on CID. We have a double goal: the identification of new genes responsible for the development of these diseases, and functional characterization of their involvement.
common feature of these diseases as well as of most other autoimmune
diseases is the strong involvement of the HLA genes and more broadly of
the major histocompatibility complex (MHC).
Because much remains to be learnt on the role of this region in
autoimmunity, we are developing specific researches on this topic by
focusing on spondylarthritis, autoimmune myasthenia gravis two diseases that show a strong association with the MHC. We are also planning to develop the same approach on rheumatoid arthritis. The team develops also research on Systemic sclerosis
(SSc) an orphan disease characterized by vascular, immune and
connective tissue anomalies. Among the many different immune-mediated
rheumatic diseases, SSc stands out as a severely incapacitating and
life-threatening disease, the pathogenesis of which is largely unknown
and for which therapeutic options are few and insufficient.
Recently, a new group has joined our team. This group develops fundamental researches on the role of the protein AIRE
in regulating the expression of a broad spectrum of auto-antigens in
the thymus. By focusing on AIRE, the main research interest of the group
is to decipher the molecular mechanisms leading to the establishment of
immune tolerance to self and therefore preventing autoimmune
manifestations and diseases.
Genetical Genomics: Starting from clinical investigations, and based on genetic and genomic approaches, we use in vitro cellular assays or suitable animal models, as needed.
The functional role of dendritic cells and myeloid suppressor cells are analysed. HLA-B27 on the one hand and clusterin and FADD on the other will be particularly studied in SpA and RA respectively. Similarly, progenitor-derived endothelial cells and genes of interest identified by genetic and other approaches will be analysed for their involvement in SSc.
Our ultimate goal is to help development of new diagnostic and therapeutic strategies based on pathophysiological grounds. The interactions between scientists and physicians in the team contribute importantly to the translation of fundamental research into clinical application. In addition our large and cohesive collaborative network should be instrumental in the future to set new therapeutic approaches. Our aim is to develop further the collaborations with clinicians to reinforce our orientation in translational medicine.
Recent major achievements:
a) Molecular signatures of chronic autoimmune diseases (Gene Immunity 2004, PNAS 2006, Arthritis Rheum 2010, 2011)
b) Identification of new susceptibility loci in autoimmune diseases (Hum Mol Genet 2004, Diabetes 2004, PNAS 2004, Arthritis Rheum 2009, 2011; Plos Genet 2009, 2011)
c) Identification of a functional defect of dendritic cells (SpA) (Arthritis Rheum 2006-2007-2008-2009-2011)
d) The self-antigen and regulation of its thymic expression in human autoimmunity (Nature 2007; (Cell 2010* post-doc in C Benoist’lab).
e) Identification of new molecular targets (Cancer Res 2004, J. Immunol 2006, JBC 2008-2010, Trends and Immunol 2010) hes. Our aim is to develop further the collaborations with clinicians to reinforce our orientation in translational medicine.