Our immune systems are sophisticated defence mechanisms which identify invading pathogens and coordinate their removal. Specialised cells known as T and B lymphocytes are key effectors of the adaptive immune response. Lymphocyte development is tightly controlled to prevent the expansion of destructive, self-reactive T and B cells and the development of autoimmune diseases. Themis, a recently described T cell specific protein, is a key regulator of T cell development. Accumulating evidence also links Themis to inflammatory diseases, such as inflammatory bowel disease, yet the structural and mechanistic basis of these functions remain poorly understood. Themis1, and the related protein Themis2, contain two copies of a newly described domain dubbed the CABIT domain, crucial for Themis activity. However, no structural information is yet available.
The objective of this research program is to provide timely insights into the structure and function of Themis1 and Themis2 and to investigate the unexplored role of these proteins in inflammatory signalling. Elucidation of Themis1 and Themis2 structural domains, particularly the CABIT domain, and how these proteins interact with key binding partners will provide insights into the function of Themis and related proteins in inflammatory pathways. We expect that our work will lead to a better understanding of Themis1 and Themis2 and impact the development of novel therapeutic strategies to target Themis activity in inflammatory diseases.