TEAM 2 - Inflammasome and ion channels

The Chamaillard's laboratory on Inflammasome and Ion Channels is interested in defining how Nods-like receptors contribute to microbial tolerance, host defence and antitumoral immunity, and how deregulation of several Nods-like receptors (including the Crohn's disease predisposing NOD2 gene) break down in Crohn's disease and colitis-associated colorectal cancer. Crohn's disease affects millions of individuals worldwide through the influence of several genetic and environmental factors. While a disproportionate immune response is found in Crohn's disease patients, our most recent studies in mice experimentally demonstrated that defects in the Crohn's disease predisposing NOD2 gene alters the functionality of the gut microbiome in a manner that it confers a risk of colitis and intestinal tumorigenesis (Couturier-Maillard et al J Clin Invest 2003). This led us to reveal an unexpected interplay with cigarette smoking that may modulate risk of developping Crohn's disease (PMID:28506689) and an impact on anti-cancer drugs efficacy as an epithelial-operating immune checkpoint (Daillere et al Immunity 2016). More recently, we recently provided evidence that NLRP12 mediated proteosomal degradation of NOD2 in monocytes promotes bacterial tolerance and colonisation in a model of enteric infection (Normand et al Nat Commun 2018).

Using a variety of techniques and complex genetic models, we have contributed to the field of mucosal immunology by identifying novel dendritic cell subsets and several pathways that underlie inflammation-driven carcinogenesis. Notably, Lionel F. Poulin contributed to a better understanding of mouse and human dendritic cells by the identification and characterization of a novel subset of dendritic cells that is involved in the generation of cytotoxic CD8+ T cells in mice and human (Poulin et al J Exp Med 2007). Encouraged by these results, our most recent work paid off by the identification of two additional regulatory pathways of NOD2 signalling that are required for the development of monocyte-derived dendritic cells (Chauvin et al., manuscript in preparation and Lasseaux et al Sci Report 2017). Meanwhile, the laboratory has also unveiled several mechanisms that are contributing to the efficacy of the wound healing process (Normand et al PNAS 2011, De Arcangelis et al Gut 2017), among which the Nod-like receptor pyrin domain-containing protein 6 that we found to be required for regulating the gut microbiota (Radulovic et al Mucosal Immunol 2018) and intracellular detection of lipoteichoic acid (Hara et al Cell 2018).

The Chamaillard's laboratory was created in 2010 with the highest possible grade (A+) by the French national research assessment agency and with an uninterrupted funding record since 2004. During the last five years, our laboratory was labelled as Equipe Fondation pour la Recherche Médicale. Since then, about 80 papers were published in peer-reviewed international journals in the field of immunology, gastroenterology and oncology, which includes about 20 cutting-edges original articles (eg. Blood Gastroenterology, Gut, Immunity, J Clin Invest, J Exp Med, Nature Medicine, Proc Natl Acad Sci U S A, Science).