Welcome to new PhD student Alessandro Cutilli

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Alessandro Cutilli recently graduated from University of Padua (Italy) and has joined the Coffer Lab to work on a collaborative project together with Caroline Lindeman’s group focusing on CD4+ T cells in graft-versus-host-disease. Graft-versus-Host-Disease is the most life-threatening complication following allogeneic hematopoietic stem cell transplantation (HSCT) where patients are transplanted with a combination of donor hematopoietic stem cells and lymphocytes. Despite treatment and prevention strategies GvHD with intestinal and liver involvement still has around a 30% mortality rate and forms a large urgent unmet medical need. Transferred alloreactive T cells respond in a complex manner, and the reasons for induction of GvHD, while involving inappropriately targeted CD4+ T cell activation, remain largely unclear and difficult to predict. Devising strategies to transiently "inactivate" T cells that mediate unwanted immune responses will have important implications for the control GvHD after bone marrow transplantation. Existing therapies, such as steroid-treatment, tend to broadly suppress undesirable immune responses, are often ineffective, and can trigger a variety of unwanted side effects. This is particularly dangerous in transplant patients who are extremely susceptible to infection. One critical control mechanism that ensures peripheral T cells avoid inappropriate activation is the induction of anergy, a hyporesponsive-state where cells don’t proliferate or produce cytokines and are more resistant to subsequent stimulation. Our recent preliminary data has shown for the first time that it is possible to induce anergy in CD4+ T cell populations by inhibiting (macro)autophagy, even in hyperactivated cells. Alessandro will be further investigating this using complex in vitro 3D cell culture systems as part of the EU COFUND RESCUE consortium.