Role of important protein improves understanding of autoimmune diseases

Researchers – led by Great Ormond Street BRC-supported Professor Tessa Crompton in collaboration with the Paediatric Department at Oxford University – have identified the role of a key protein in normal development of the thymus, an important organ of the immune system. The protein, known as Sonic hedgehog (SHH), is one of a few factors that regulate thymic epilthelial cell (TEC) differentiation and lineage choice. These findings contribute to our understanding of human autoimmune diseases and will inform strategies to replace thymus function in athymic children.

TECs are an essential component of the thymic stroma and are required to support T cell development. Two broad categories of TEC exist; medullary TECs, which are essential for the induction of tolerance to self, and cortical TECs, which are essential for T cell fate specification and T cell receptor repertoire selection. Researchers used both adult and foetal TECs to show that SHH regulates medullary TEC differentiation and function, with the potential to alter central tolerance.

These findings are important to our understanding of immunity, autoimmunity and immunodeficiency. In the future it will be important to assess the effects of SHH signalling on the induction and severity of human autoimmune diseases.

These findings were published in the Journal of Autoimmunity.