The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection.
J Exp Med
; 212(12): 2041-56, 2015 Nov 16.
Article
en En
| MEDLINE
| ID: mdl-26503446
ABSTRACT
The transcription factor T-bet is critical for cytotoxic T lymphocyte (CTL) differentiation, but it is unclear how it operates in a graded manner in the formation of both terminal effector and memory precursor cells during viral infection. We find that, at high concentrations, T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally differentiated states. ZEB2 and T-bet cooperate to switch on a terminal CTL differentiation program, while simultaneously repressing genes necessary for central memory CTL development. Chromatin immunoprecipitation sequencing showed that a large proportion of these genes were bound by T-bet, and this binding was altered by ZEB2 deficiency. Furthermore, T-bet overexpression could not fully bypass ZEB2 function. Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitment of CTLs to terminal differentiation, thereby restricting their memory cell potential.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Linfocitos T Citotóxicos
/
Diferenciación Celular
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Proteínas de Homeodominio
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Proteínas de Dominio T Box
/
Coriomeningitis Linfocítica
Límite:
Animals
Idioma:
En
Revista:
J Exp Med
Año:
2015
Tipo del documento:
Article