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Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.
Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow. The Journal of experimental medicine Yu, V. W., Saez, B., Cook, C., Lotinun, S., Pardo-Saganta, A., Wang, Y. H., Lymperi, S., Ferraro, F., Raaijmakers, M. H., Wu, J. Y., Zhou, L., Rajagopal, J., Kronenberg, H. M., Baron, R., Scadden, D. T. 2015Abstract
Production of the cells that ultimately populate the thymus to generate a/ß T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn(+) cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell-based adaptive immunity.
View details for DOI 10.1084/jem.20141843
View details for PubMedID 25918341