Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.
J Exp Med
; 212(5): 759-74, 2015 May 04.
Article
en En
| MEDLINE
| ID: mdl-25918341
ABSTRACT
Production of the cells that ultimately populate the thymus to generate α/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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Timo
/
Células de la Médula Ósea
/
Linfocitos T
/
Péptidos y Proteínas de Señalización Intracelular
/
Células Madre Mesenquimatosas
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2015
Tipo del documento:
Article