The First In Vivo Exploration of Interleukin 38

Project Description: Direct clinical relevance: medium. Hands-on learning opportunities: Various aspects of work with mice and patient samples, workup of tissues for various downstream applications, flow cytometry, histology, immunohistochemistry, protein detection by ELISA, RNA detection by real-time PCR. Interleukin (IL)-38 is a novel member of the IL-1 family of cytokines. The majority of IL-1 family members play important roles in inflammatory diseases – either as promoters or inhibitors of inflammation. IL-38, however, received almost no research attention until our group renamed the new IL-1 family cytokines in 2010. Thus, its function is still largely unknown. Recently, we discovered that IL-38 plays a role in systemic lupus erythematosus (SLE) – a very severe and potentially fatal autoimmune disease that mainly affects young women in their childbearing age. We found that SLE patients have elevated serum IL-38 concentrations and that IL-38 is predictive of disease severity and the development of major SLE-associated complications. Moreover, we have shown in vitro that IL-38 has anti-inflammatory properties and inhibits the production of cytokines that promote inflammation. Now, we want to investigate the function of IL-38 in vivo. For this purpose, we have generated the very first IL-38 knockout mouse that is not available anywhere else in the world. In this exciting project we will undertake the first experiments using this mouse in a murine model of SLE but will also perform experiments on blood samples directly obtained from SLE patients. Applying techniques such as ELISA, flow cytometry, real-time PCR and histology we will aim to identify the role of IL-38 in SLE and potentially lay the foundation for a novel therapeutic approach for the treatment of SLE.