Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function.
Elife
; 122024 Apr 24.
Article
en En
| MEDLINE
| ID: mdl-38655862
ABSTRACT
Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene (Ikzf1). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling. While Ikzf1-Treg-cko mice do not develop spontaneous autoimmunity, Ikaros-deficient Treg are unable to control conventional T cell-mediated immune pathology in response to TCR and inflammatory stimuli in models of IBD and organ transplantation. These studies establish Ikaros as a core factor required in Treg for tolerance and the control of inflammatory immune responses.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
/
Linfocitos T Reguladores
/
Factor de Transcripción Ikaros
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Factores de Transcripción Forkhead
Límite:
Animals
Idioma:
En
Revista:
Elife
/
ELife (Cambridge)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos