Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells.

Abstract:

:Interferon regulatory factor (IRF) 4 is a member of the IRF family of transcription factors and plays critical roles in the development of CD4(+) T cells into Th2 and Th17 cells. Using the infection model of Nippostrongyrus brasiliensis, we have confirmed the critical roles of IRF-4 in Th2 development in vivo by using IRF-4(-/-) BALB/c mice. However, naïve IRF-4(-/-)CD4(+) T cells produced Th2 cytokines, including IL-4, IL-5, and IL-10, but not IL-2 or IFN-gamma, at levels higher than wild-type BALB/c CD4(+) T cells in response to T cell receptor stimulation. In contrast, effector/memory IRF-4(-/-)CD4(+) T cells did not exhibit increased production of Th2 cytokines. Knockdown of IRF-4 expression by using small interfering RNA promoted IL-4 production in naïve CD4(+) T cells but inhibited it in effector/memory CD4(+) T cells. These results indicate that IRF-4 plays differential roles in the regulation of Th2 cytokine production in naïve CD4(+) T cells and effector/memory CD4(+) T cells. IRF-4 inhibits Th2 cytokine production in naïve CD4(+) T cells, whereas it promotes Th2 cytokine production in effector/memory CD4(+) T cells.

authors

Honma K,Kimura D,Tominaga N,Miyakoda M,Matsuyama T,Yui K

doi

10.1073/pnas.0803171105

subject

Has Abstract

pub_date

2008-10-14 00:00:00

pages

15890-5

issue

41

eissn

0027-8424

issn

1091-6490

pii

0803171105

journal_volume

105

pub_type

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