Chemotaxis-induced phase separation in the thymus

Henrik Weyer (Postdoc KITP)

Title: Chemotaxis-induced phase separation in the thymus

Abstract: 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 show that the cross-talk between negatively selected thymocytes and medullary-tissue cells enables the mouse thymus to
self-organize into this segregated structure, which allows for efficient T-cell (negative) selection [1]. To better understand the properties of the resulting cortex–medulla structure, we theoretically analyze Keller–Segel models that capture the core mechanisms of chemotactic aggregation in diverse systems. We demonstrate that chemotactic aggregation can be understood using a generalized Maxwell construction based on the balance of density fluxes and reactive turnover. This formulation implies that aggregates generically undergo coarsening, which is interrupted and reversed by cell growth and death. Together, both stable and spatiotemporally dynamic aggregates emerge. Our theory mechanistically links chemotactic self-organization to phase separation and reaction–diffusion patterns [2].

[1] D Muramatsu, HW, et al. (2025) Basic interactions responsible for thymus function explain the convoluted medulla shape. PNAS 122(25), e2415288122.
[2] HW, D Muramatsu, and E Frey (2024) Chemotaxis-induced phase separation. arXiv:2409.20090 (accepted in PRL).