Laure Dumoutier

Major achievements

• Discovery of IL-22 and its soluble receptor, IL-22BP
• Demonstrate the role of IL-22 in skin inflammatory diseases such as psoriasis
• Price Maggy et Robert de Hovre

Question

How IL-10-related cytokines can modulate skin and gut inflammatory diseases such as psoriasis or inflammatory bowel disease, and how they could be used as targets for therapy in these pathologies.

Research focus

Psoriasis, pancreatitis and colitis (or Crohn's disease) are three inflammatory diseases affecting the skin, pancreas and intestinal mucosa respectively. They result from inappropriate activation of the innate and adaptive immune systems, accompanied by an imbalance in the production of cytokines.

IL-22 exacerbates psoriatic skin lesions. Following an insult to the keratinocytes, dendritic cells become activated and migrate to the lymph nodes, where they will undergo Th17 and Th22 differentiation. These cells, together with γδ T cells and ILC3, will produce IL-22. IL-22 in turn acts on keratinocytes to induce proliferation leading to acanthosis, inhibit differentiation leading to parakeratosis and finally induce chemokine production recruiting many inflammatory cells to the skin. Acanthosis, parakeratosis and inflammation are hallmarks of psoriatic skin.

Cytokines are molecules produced by cells such as lymphocytes in response to a stimulus. These proteins target different cell types that express their specific receptors. They play an important role in the host's inflammatory response to infection. However, excessive inflammation is also thought to underlie many diseases.

Laure Dumoutier and her laboratory are particularly interested in deciphering the mechanisms by which cytokines can modulate the inflammatory response and control or exacerbate certain diseases that affect the skin, the pancreas or the intestine. We are particularly interested in IL-22, a cytokine discovered in the laboratory. Various cell types produce this cytokine in response to inflammatory stimuli. To exert its activity, this cytokine binds to a receptor (IL-22R) that can also mediate the activities of IL-24, another member of the IL-10 cytokine family. IL-22 acts on non-immune cells such as lung and intestinal epithelial cells and keratinocytes, exerting either pro- or anti-inflammatory effects depending on the disease. The main goal of our laboratory is to elucidate the respective roles of IL-22, IL-24 and IL-22R in different mucosal inflammatory diseases by taking advantage of IL-22- and IL-22R-deficient mice generated in the host laboratory.

Through these studies, Laure and her team hope to develop new targeted therapies for skin or gut diseases.

Projects

• Inflammatory bowel disease and its skin inflammatory comorbidities: from GWAS-identified genes to their function in immune and epithelial cells
• Role of IL-22 in pancreatic tumor development
• Characterization of and role of IL24 in skin tumor
• Characterization of IL-20R signaling and its role in central nervous system
• Role of C-terminal part of IL-22R in inflammatory disorders

Laure Dumoutier obtained her Master's degree in Biomedical Sciences from UCLouvain (Belgium) in 1997. She joined the laboratory of Prof. Jean-Christophe Renauld at the Brussels branch of the Ludwig Institute, where she obtained her PhD in Biomedical Sciences in 2002. Her work has focused on the family of IL-10 related cytokines, in particular IL-22. She discovered mouse IL-22 and its human orthologue. She discovered a soluble receptor for IL-22 that blocks its activity. She highlighted a new mode of activation of the JAK-STAT pathway that is independent of tyrosine residues in the IL-22 receptor. In 2008, she became an F.R.S-FNRS researcher and associate professor at UCLouvain. In 2010, she set up her own group at the de Duve Institute. Laure and her team characterised the pro-inflammatory role of IL-22 in mouse models of psoriasis and started a strong collaboration with the Dermatology Department of the Saint Luc Hospital. Since 2020, Laure has been an F.R.S-FNRS Senior Research Associate at UCLouvain. Her group continues to study the role of IL-22, IL-24 and IL-22R in various mucosal inflammatory diseases.

Honors

• International Cytokine Society (ICS) outstanding scholar award
• Price Maggy and Robert de Hovre

Affiliations

• Senior Research associate of the F.R.S-FNRS
• Professor Part time UCLouvain, de Duve institute