The CXC-chemokine receptor 4 (CXCR4) provides essential signals that guide thymocytes on their developmental journey through the thymus, according to a recent study in The Journal of Immunology.

As thymocytes mature in the post-natal thymus they migrate from their entry point near the cortico-medullary junction (CMJ), outwards across the cortex towards the capsule, and then back again across the cortex towards the medulla. This migration enables these developing progenitor cells to interact with thymic stromal cells that provide signals that are required for commitment to the T-cell lineage, and for efficient thymocyte differentiation and proliferation.

How is this cortical migration controlled? Petrie and colleagues investigated the role of chemokines in this process by first asking which chemokine receptors were expressed by thymocyte progenitors. Of all of the known chemokine receptors, CXCR4 was the most abundant, being expressed by all thymocyte prognenitors. Further experiments showed that the ligand for this receptor, CXCL12, is produced by cortical stromal cells, indicating that signals through CXCR4–CXCL12 could potentially be involved in guiding progenitors into the cortex.

To investigate this possibility, the authors next measured whether thymocyte progenitors could migrate in response to CXCL12. Transwell migration assays using CXCL12 as a chemoattractant showed that all populations of progenitors that were tested migrated towards CXCL12. To confirm the role of CXCR4 signalling in this directional movement, the in vivo migration of CXCR4-deficient progenitor thymocytes was assessed. T-cell numbers were low and thymocyte differentiation was blocked at an early stage in mice reconstituted with bone marrow that lacked CXCR4 expression. Furthermore, thymocytes derived from CXCR4-deficient bone marrow accumulated at the CMJ and did not migrate efficiently into the cortex.

This study highlights the essential and non-redundant role for CXCR4–CXCL12 signalling in controlling the migration of thymocyte progenitors across the cortex — a process that is required for the development of mature T cells in the post-natal thymus.