TY - JOUR
T1 - Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow
AU - Yu, Vionnie W.C.
AU - Saez, Borja
AU - Cook, Colleen
AU - Lotinun, Sutada
AU - Pardo-Saganta, Ana
AU - Wang, Ying Hua
AU - Lymperi, Stefania
AU - Ferraro, Francesca
AU - Raaijmakers, Marc H.G.P.
AU - Wu, Joy Y.
AU - Zhou, Lan
AU - Rajagopal, Jayaraj
AU - Kronenberg, Henry M.
AU - Baron, Roland
AU - Scadden, D. T.
N1 - Publisher Copyright:
© 2015 Yu et al.
PY - 2015/5/4
Y1 - 2015/5/4
N2 - Production of the cells that ultimately populate the thymus to generate α/β 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.
AB - Production of the cells that ultimately populate the thymus to generate α/β 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.
UR - http://www.scopus.com/inward/record.url?scp=84930678351&partnerID=8YFLogxK
U2 - 10.1084/jem.20141843
DO - 10.1084/jem.20141843
M3 - Article
C2 - 25918341
AN - SCOPUS:84930678351
VL - 212
SP - 759
EP - 774
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 5
ER -