MD TP65: Expression of AT1R, ETAR, CXCR3 and CXCR4 in lung tissue of the ApoE-knockout mouse model after transfer of autoantibodies

Autoantibodies recognising different G Protein-coupled receptors (GPCR) are found in patients suffering from rheumatic diseases such as systemic sclerosis (SSc) as well as in healthy people, forming specific regulatory networks. It has been shown that some of these autoantibodies function as biomarker, e. g. low concentrations of anti-CXCR3- and anti-CXCR4-antibodies (ab) predict a deterioration of lung function of SSc patients, whereas high amounts of these autoantibodies correspond to a stable lung function. The autoantibodies targeting GPCR seem to have functional (patho)physiological roles and therefore might present a possible therapeutic target.
Because SSc patients have a higher prevalence of a subclinical atherosclerosis and similar pathophysiological mechanism are involved, the aim of this project is to analyse the expression of four selected GPCR, i.e. Angiotensin II type 1 receptor (AT1R), Endothelin receptor type A (ETAR), CXCR3 and CXCR4 in lung tissue of the Apoe-Knockout mouse model after passive transfer of human immunoglobulin G (IgG) containing autoantibodies directed against the four receptors derived from SSc patients and from healthy donors. Accordingly, the expression of AT1R, ETAR, CXCR3 and CXCR4 will be investigated via quantitative real-time polymerase chain reaction (qPCR) and via immunohistochemistry or immunofluorescence staining.