A model developed by LMU biophysicists demonstrates how biological processes form the convoluted internal architecture of the thymus – allowing for better suppression of autoimmune responses.

The thymus is one of the most important organs of the immune system, where T cells learn to distinguish the body’s own tissue from foreign tissue – a decisive step in preventing autoimmune diseases. The complex internal shape of the thymus is remarkable, with a highly convoluted structure in the region of the medulla. Scientists have been unsure how this complicated structure arises and whether its genesis is related to the function of the organ.

A team led by LMU biophysicist Professor Erwin Frey has now developed a theoretical model based on signaling pathways in the thymus which they experimentally demonstrated in mice. The model mirrors the development of the unusual morphology of the medulla and proposes that the convoluted form of the thymus results directly from the biological interactions necessary for its function.

The key lies in a particular type of feedback known as thymic cross-talk: T cells are immunologically primed in the thymus through exposure to various antigens. In the medulla, the body tests whether the cells respond to its own antigens – if so, these cells are eliminated. While they are being eliminated, the cells emit signals that prompt the surrounding tissue to grow. The growing tissue in turn influences where further T cells are tested. “A self-organized, convoluted structure emerges from this interaction,” says Frey. “This architecture allows the organ to function more efficiently. A round thymus would be less efficient in the elimination of autoreactive T cells.”

These findings could also be significant for other organs beyond the thymus, emphasize the authors. The model illustrates how biological function can form spatial structures – and thus generates an organ morphology that is deeply rooted in function. It not only predicts known observations – such as the changes in thymus structure in the case of genetic mutations – but also furnishes new, experimentally testable hypotheses.