Targeting TGF-β1, β2 or β3 activation in auto-immunity and graft-versus-host disease
auto-immune diseases • immunology • cytokines
Sophie Lucas is professor at the Université catholique de Louvain. Her work at the de Duve Institute focuses on the mechanisms whereby Regulatory T cells (Tregs) inhibit the immune system, preventing it from attacking healthy tissue. An insufficient activity of Tregs might lead to auto-immune diseases, as well as to the rejection of grafts or graft-versus-host diseases. Conversely, an excessive activity of Treg lymphocytes blocks anti-tumour immune responses and contributes to cancer progression. Sophie Lucas and her team have found that Treg lymphocytes produce active TGF-β1, a cytokine known for its immuno-suppressive properties. Among the 3 isoforms of TGF-β, TGF-β1 is the main form expressed
by immune cells.
This WELBIO projects aims to develop antibodies able to activate TGF-β1 and to assess (in preclinical models) if these antibodies can treat auto-immune or graft-versus-host diseases. The cellular origin of TGF-β1 will be investigated in a model of Systemic Lupus Erythematosus, a chronic auto-immune disease which can affect multiple organs. Treg lymphocytes might express and activate TGF-β1 in other cells to block auto-immune reactions. A second part of the project will be dedicated to Systemic Scleroderma, an auto-immune disease characterised by a profound fibrosis which could be linked to an excessive activation of one of the TGF-β isoforms.