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.