Interferon regulatory factor 4 differentially regulates the production of Th2 cytokines in naive vs. effector/memory CD4+ T cells.
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.
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
Kiri
K
Honma
Daisuke
D
Kimura
Norio
N
Tominaga
Mana
M
Miyakoda
Toshifumi
T
Matsuyama
Katsuyuki
K
Yui
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000276:immunology*; D007156:Immunologic Memory; D050835:Interferon Regulatory Factors / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018418:Th2 Cells / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
D016207:Cytokines; D050835:Interferon Regulatory Factors; D000099218:Interferon Regulatory Factor-4