Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.
Bottom Line: 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.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.
Affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02215 Harvard Stem Cell Institute, Cambridge, MA 02215 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02215.Show MeSH
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Mentions: We tested whether Notch ligand expression specifically by Ocn+ cells caused the lymphopoietic phenotype using the conditional OcnCreER;DLL4Fl/Fl strain. Ocn+ cell-specific DLL4 deletion resulted in significantly reduced Notch-activated CLP, T cell–competent Ly6D−-CLP, and CCR7-expressing Ly6D−-CLP (Fig. 6 A, discussed in the following paragraphs), with a decrease comparable in magnitude to that seen with Ocn+ cell depletion (Fig. 2 B). Thymic intermediates and blood T-lymphocytes were also decreased (Fig. 6 A).
Affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02215 Harvard Stem Cell Institute, Cambridge, MA 02215 Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02215.