Rantes/Ccl5 influences hematopoietic stem cell subtypes and causes myeloid skewing.
Blood
; 119(11): 2500-9, 2012 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-22289892
ABSTRACT
HSCs undergo dramatic changes with aging. An increase in absolute numbers of HSCs along with a functional deficit in reconstitution potential and a shift toward production of myeloid cells are the hallmarks of murine hematopoietic aging. Here, we show that high levels of the inflammatory cytokine Rantes are found in the aging stem cell milieu. Forced overproduction of Rantes by retroviral expression in BM progenitors resulted in a deficit of T-cell output, and brief ex vivo exposure of HSCs to Rantes resulted in a decrease in T-cell progeny concomitant with an increase in myeloid progenitors. In contrast, Rantes knockout (KO) animals exhibit a decrease in myeloid-biased HSCs and myeloid progenitors and an increase in T cells and lymphoid-biased HSCs. KO HSCs retained their HSC subtype distribution and they produced more lymphoid-biased HSCs in transplantations. Rantes deficiency also resulted in a decreased mammalian target of rapamycin (mTOR) activity in KLS cells. In a heterochronic transplantation setting, we further show that aged HSCs placed in a young environment generate less myeloid cells. These data establish a critical role for environmental factors in the establishment of the aged-associated myeloid skewing phenotype, which may contribute to age-associated immune deficiency.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Linfócitos T
/
Senescência Celular
/
Quimiocina CCL5
/
Células Progenitoras Mieloides
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Blood
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos