Basic interactions responsible for thymus function explain the convoluted medulla shape

The thymus organ produces and selects nascent T cells (thymocytes) to establish a competent T cell repertoire, which is a central component of the adaptive immune system. Thymocyte production and (negative) selection occur in two spatially segregated tissues, the cortex and medulla, which in mice are intertwined in a convoluted spatial structure. By modeling the central, experimentally verified cell–cell signaling pathways, we demonstrate that the cross-talk between negatively selected thymocytes and medullary tissue cells enables the mouse thymus to self-organize into this segregated structure. The cross-talk acts as a feedback mechanism that ensures the robust organization of a spatial structure, allowing the efficient negative selection of thymocytes. Thus, in the model, form follows function because function elicits form.

D Muramatsu, H Weyer, F Gartner, E Frey (2025). Basic interactions responsible for thymus function explain the convoluted medulla shape, PNAS 122(25), e2415288122, doi:10.1073/pnas.2415288122.