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Nico Ghilardi Scientist: Molecular Biology |
"My lab is interested in the biology of cytokines, as they are often implicated in human immune disease. Cytokines and their receptors represent excellent targets for pharmacological intervention, not only because they are accessible to protein therapeutics, but also because many of them have very specific biological functions. We have specifically focused on IL-27, IL-23, and IL-31 over the past few years.
IL-27 is a cytokine with pro- and anti-inflammatory activities. It has profound effects on T-helper cell fate decisions, as it can promote the TH1 and suppress the TH17 phenotype. In vivo, IL-27 acts as an immune suppressor in some models of infectious and autoimmune disease, but paradoxically, it also is critically required for disease pathogenesis in other models. None of the known in vitro activities of IL-27 can fully explain the various phenotypes of IL-27R deficient mice.
IL-23 is interesting because it is required for pathogenesis in many models of autoimmune disease. It has recently attracted a lot of attention because the IL-23 receptor is genetically implicated in human Crohn's disease, a debilitating inflammatory condition. Mechanistically, it is not clear how polymorphisms in the IL-23R gene cause disease. While IL-23 can act as a survival factor for pathogenic TH17 cells, it also has effects on non-T cells. This is an area of active investigation in my lab.
IL-31 is a TH2 derived cytokine that acts on activated antigen presenting cells. One of its functions is to limit TH2 mediated inflammation; besides that, it also has stimulatory effects on bone marrow stem cells. We are continuing to explore its biology."