From the Bone Marrow to the Thymic Niche

Abstract

To generate T cells throughout adult life, the thymus must import hematopoietic progenitor cells from the bone marrow via the blood. The cellular and molecular mechanisms governing the circulation of thymus-seeding progenitor cells are well characterized in mice but not in humans. The aim of the present study was to characterize the molecular mechanisms and cellular components involved in thymus colonization by lymphoid progenitors (CD34+/CD10+/CD7-/CD24-) and the early steps of thymopoiesis under physiological conditions in humans. Our results demonstrate that circulating lymphoid progenitor cells express CCR9 and CXCR4 chemokine receptors, VLA-4, VLA-5 and VLA-6 integrins and PSGL-1 and CD44 adhesion molecules. We used in vitro migration and adhesion assays to validate the functional status of these markers.As in the mouse, human circulating progenitor cells enter the thymus at the corticomedullary junction (CMJ). Once in the thymus, crosstalk with thymic epithelial cells causes the circulating progenitors to commit to the T-cell differentiation pathway. In order to characterize thymic niches and interactions between circulating progenitors and the thymic stroma, we undertook a chemokine/chemokine-receptor-focused gene expression analysis of sorted lymphoid progenitor cells and CMJ epithelial cells (based on the expression of EpCAM and Delta-like-4). We observed an unexpected gene expression profile for chemokines and chemokine regulators in thymus-seeding CD34+/CD10+/CD7-/CD24- cells and epithelial cells at the CMJ. The present results should help us to highlight candidate genes involved in the early steps of human thymopoiesis. DisclosuresNo relevant conflicts of interest to declare.