Regulatory T-cells in the context of SSc and autoimmunity
This project aims at studying the interaction between the affected tissues in SSc and the autoreactive immune cells. The focus lies on regulatory T (Treg) cells that are crucial in keeping autoreactive immune cells under control.
We assume that Treg cells are functionally or quantitatively decreased in SSc. Therefore in vitro culturing of Treg cells and infusion into patients and/or in vivo expansion of Treg cells using selective interleukin-2 (IL-2)-antibody complexes might improve disease. This therapy might be applicable also to other rare diseases where a weakening of Treg cells is suspected, including primary immunodeficiency syndromes with immune dysregulation. Additionally it might be useful for treatment after hematopoietic stem cell transplantation, including patients suffering from rare diseases, where chronic graft-versus-host disease develops.
In order to test these hypotheses, we will perform T reg gain and loss of function experiments in three mice models of SSc, and the impact on fibrosis and vasculopathy will be assessed. The Bleomycin and the Tsk-1 models will be used to study respectively the early inflammatory and later non-inflammatory stages of the disease. Finally the Fra-2 transgenic mice will allow us to study the vascular features of SSc.