NF90 regulates inducible IL-2 gene expression in T cells.

NF90 regulates inducible IL-2 gene expression in T cells. Research Abstract Details 

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NF90 regulates inducible IL-2 gene expression in T cells. Abstract Text:

Lingfang Shi,Wayne R Godfrey,Joseph Lin,Guohua Zhao,Peter N Kao,Lingfang Shi,Wayne R Godfrey,Joseph Lin,Guohua Zhao,Peter N Kao,

Activation of T cells induces the production of T cell growth and survival factor interleukin (IL) 2. Regulatory T cells intrinsically fail to induce IL-2 expression upon activation and can suppress IL-2 production in conventional T cells. Thus, the control of IL-2 expression is critically important to T cell immune responses, yet the mechanisms remain incompletely understood. Nuclear factor (NF) 90 is a zinc-finger DNA- and double-stranded RNA-binding protein subunit that binds specifically to the antigen receptor response element (ARRE)/NF of activated T cells target sequence in the IL-2 proximal promoter. Inducible binding of NF90 to the IL-2 promoter in vivo is shown by chromatin immunoprecipitation. NF90 gene-targeted mice exhibit perinatal lethality. Compared with newborn NF90(+/+) mice, newborn NF90(-/-) mice demonstrate severe impairment of IL-2 expression. Compared with wild-type cells, T cells deficient in NF90 are impaired in ARRE and IL-2 transcriptional activation and IL-2 mRNA stabilization. Fetal liver cells from NF90 gene-targeted mice were transplanted into irradiated adult recombination activating gene (RAG)-2(-/-) and IL-2Rgamma(-/-) mice deficient in T cells, B cells, and natural killer cells. NF90(+/+)- and NF90(-/-)-RAG chimeric mice showed grossly normal repopulation of the thymus and spleen, but only NF90(-/-) T cells were severely impaired in IL-2 gene expression. Compared with littermates, NF90(-/-) RAG chimeric mice exhibited profound T cell lymphocytopenia in the peripheral circulation. Thus, NF90 regulates inducible IL-2 transcription, mRNA stability, and gene expression in T cells and represents a novel therapeutic target for the modulation of T cell immune responses.

NF90 regulates inducible IL-2 gene expression in T cells. Publishing Authors By Initials

L Shi,WR Godfrey,J Lin,G Zhao,PN Kao,L Shi,WR Godfrey,J Lin,G Zhao,PN Kao,

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NF90 regulates inducible IL-2 gene expression in T cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of experimental medicine

VOLUME: 204

Page Numbers: 971-7

Journal Abbreviation: J. Exp. Med.

ISSN: 0022-1007

DAY: 30

MONTH: 04

YEAR: 2007

NF90 regulates inducible IL-2 gene expression in T cells. Information

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LANGUAGE: eng

NlmUniqueID: 2985109

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Grant and Affiliation Information for NF90 regulates inducible IL-2 gene expression in T cells.

AFFILIATION: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA 94305, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL62588

ACRONYM: HL

MEDLINETA: J Exp Med

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