| Project Detail |
Systemic Lupus erythematosus (SLE) is an autoimmune disease with a complex pathogenesis. Immune complexes (ICs) are formed and deposited in various tissues, leading to inflammation and damage. T cells are part of the adaptive immune system, but also express innate-like receptors that could interact with ICs by binding complement factors or the constant region of immunoglobulins. However, the extent of these interactions and there relevance for the SLE pathogenesis has not been investigated so far. In the TICI-SLE project, we will analyze these interactions by 1) investigating the expression of receptors that could interact with ICs on T cells in the blood and inflamed tissue of SLE patients, 2) cultivating T cells with immune complexes and antibodies stimulating or blocking individual receptors, thereby elucidating the consequences of these interactions and 3) analyzing spatial T cell/IC interactions and their secondary consequences (like proinflammatory changes in stromal cells and chemoattraction of inflammatory cells) in skin samples from SLE patients. We hypothesize that T cell/IC interactions result in (co-)stimulation of T cells, leading to production of proinflammatory cytokines, cytotoxicity and induction of an inflammatory microenviornment. Understanding these interactions can then be exploited by the future development of therapeutics targeting these interactions. An additional focus of the project will be the personal development of the applicant and the dissemination and exploitation of project results. |
