Requirement of GATA-binding protein 3 for II13 gene expression in IL-18-stimulated Th1 cells.
Recent reports have revealed that CD4(+) T(h) cell subsets have the ability to alter their gene expression pattern in response to extracellular stimuli. We previously highlighted the plasticity of T(h)1 cells by demonstrating that T(h)1 cells gain the capacity to produce IL-3, IL-9, IL-13 and granulocyte macrophage colony-stimulating factor in response to antigen, IL-2 and IL-18, and based on their unique function, we designated these activated T(h)1 cells as 'super T(h)1 cells'. However, the precise molecular mechanism underlying IL-13 production by super T(h)1 cells has not been elucidated. Here, we show that the GATA-binding protein 3 (Gata3) is essentially required for II13 gene expression in super T(h)1 cells. Gata3 is synergistically induced in T-box expressed in T-cells (T-bet)-expressing T(h)1 cells when co-stimulated with anti-CD3, IL-18 and IL-4 through the activation of nuclear factor of activated T cells, nuclear factor kappa-light-chain-enhancer of activated B cells and signal transducer and activator of transcription 6, respectively. However, Gata3 induction is not satisfactory, and additional TCR or anti-CD3 signaling is prerequisite for triggering IL-13 production by Gata3 plus T-bet-expressing T(h)1 cells. These findings suggest that Gata3, which is not originally expressed in T(h)1 cells, alters the cytokine production profile by T(h)1 cells.
Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Masakiyo
M
Nakahira
Kenji
K
Nakanishi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics*; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000819:agonists; D050800:STAT6 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation; D000098815:T-bet Transcription Factor
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D018793:Interleukin-13; D020382:Interleukin-18; D011948:Receptors, Antigen, T-Cell; D050800:STAT6 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor