Activating Transcription Factor 3 Is a Positive Regulator of Human IFNG Gene Expression

  • Filén S
  • Ylikoski E
  • Tripathi S
  • et al.
36Citations
Citations of this article
50Readers
Mendeley users who have this article in their library.

Abstract

IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-α in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-α, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4+ Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-α, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4+ T cells enhanced the production of IFN-γ, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-γ production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4+ T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation.

Cite

CITATION STYLE

APA

Filén, S., Ylikoski, E., Tripathi, S., West, A., Björkman, M., Nyström, J., … Lahesmaa, R. (2010). Activating Transcription Factor 3 Is a Positive Regulator of Human IFNG Gene Expression. The Journal of Immunology, 184(9), 4990–4999. https://doi.org/10.4049/jimmunol.0903106

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free