Kurzfassung

Systemic lupus erythematodes is an autoimmune disease that can involve every organ like brain, heart and kidney. The kidney involvement (nephritis) occurs in a large proportion of patients with lupus (30%-50%). Even with optimal immunsuppressive therapy, up to 25% of these patients progress to end stage renal disease. Thus, nephritis is a major cause of morbidity and mortality in lupus. Identifying molecules that mediate experimental lupus nephritis may uncover therapeutic targets and...Systemic lupus erythematodes is an autoimmune disease that can involve every organ like brain, heart and kidney. The kidney involvement (nephritis) occurs in a large proportion of patients with lupus (30%-50%). Even with optimal immunsuppressive therapy, up to 25% of these patients progress to end stage renal disease. Thus, nephritis is a major cause of morbidity and mortality in lupus. Identifying molecules that mediate experimental lupus nephritis may uncover therapeutic targets and biomarkers. Macrophages (Mø) are prominent in the kidney and mediate renal destruction in lupus. Mø express the CSF-1R, the receptor for Colony Stimulating Factor 1 (CSF-1). Our studies have highlighted CSF-1, the principle molecule required for Mø survival and proliferation, as an appealing therapeutic target. CSF-1 is upregulated in the Mø-rich kidney during lupus and mediates renal destruction in lupus-susceptible, MRL-Faslpr mice. Based on studies in CSF-1-Rdeficient mice, the actions of CSF-1 are exclusively mediated via CSF-1R. However, CSF-1R deficient mice develop a more severe phenotype than mice lacking CSF-1 (Csf1op/op).  This led to the discovery of a second ligand for CSF-1R, interleukin 34 (IL-34).
Therefore,  the goal of this proposal ist to determine if CSF-1 and IL-34 have distinct and shared function in the pathogenesis of SLE using the MRL-Faslpr mouse model and transfer the data to human SLE. Taken together, CSF-1 and IL-34 may have distinct functions in the pathogenesis of diseases such as lupus and our data will help to generate potential therapeutic options/targets or to find a distinct biomarker for SLE manifestions and/or activity.» weiterlesen» einklappen