Downregulation of NFAT3 Due to Lack of T-Box Transcription Factor TBX5 Is Crucial for Cytokine Expression in T Cells.

The NFAT family transcription factors play crucial roles in immunological and other biological activities. NFAT3 is rarely expressed in T cells, and the mechanisms and significance of the specific NFAT3 downregulation in T cells have been unknown. In human CD4 T cells, overexpression of NFAT1 and NFAT3 enhanced and suppressed IL-2 expression, respectively.

Protein phosphatase 1 is involved in IL-2-induced IL-5 and IL-13 expression in human T cells.

IL-2 plays an important role in immunological and other biological functions. This cytokine directly induces the production of several cytokines, such as IL-5 and IL-13. The mechanisms of IL-2-mediated cytokine synthesis are mostly unclear; however, the involvement of IL-2 receptor (IL-2R)β has been suggested.

NFAT1 and NFAT2 differentially regulate IL-17A expression in human T cells.

Background: The NFAT family transcription factors play crucial roles in T cell functions. Recently, NFAT has been implicated in the production of an inflammatory cytokine, IL-17A; however, functional differences among NFAT members in IL-17A synthesis have not been elucidated. In this study, the relative contribution of NFAT1 and NFAT2 to IL-17A expression in human T cells was investigated.

Zinc finger protein, multitype 1, suppresses human Th2 development via downregulation of IL-4.

Background: Among several GATA family transcription factor-associating proteins, zinc finger protein, multitype 1 (ZFPM1), at least that of murine origin, has been shown to modulate the activity of GATA-3. However, the functional role of human ZFPM1 in the immune system has not been elucidated. Therefore, we here investigated the contribution of ZFPM1 to human Th1/Th2 differentiation.

Selective down-regulation of Th2 cytokines by C-terminal binding protein 2 in human T cells.

Background: Among several C-terminal binding proteins (CtBPs), friend of GATA (FOG) has been implicated in the down-regulation of GATA-3-mediated Th2 cell differentiation. Here we investigated the role of CtBP2 in Th1 and Th2 cytokine expression in human T cells.

Methods: CtBP2 was introduced into human peripheral CD4+ T cells by a lentiviral transduction system.

Proteomic Approach to FcepsilonRI aggregation-initiated signal transduction cascade in human mast cells.

Background: Mast cells (MCs) play a central role in allergic reactions through high-affinity IgE receptor (FcepsilonRI)-mediated responses. Many attempts have been performed to investigate MC functions, though molecular bases of the intracellular signaling cascade through FcepsilonRI, especially in human MCs, remain scant and unexplored.

Methods: Human MCs were differentiated from CD34+ cells by culture with stem cell factor, IL-6 and IL-3.

T-box 21 transcription factor is responsible for distorted T(H)2 differentiation in human peripheral CD4+ T cells.

Background: Regardless of T(H)1/T(H)2 theory, CD4(+) T cells of patients with allergic asthma, a typical T(H)2 disease, and those of healthy subjects expressed equivalent levels of IFN-gamma, even though T(H)2 cytokines were significantly upregulated in asthmatic patients.

Objective: The mechanisms underlying distorted T(H)2 cell polarization in human T cells were elucidated.

Methods: Cytokine-producing activity and the expression of T(H)1/T(H)2-specific transcription factors in naïve, T(H)1/T(H)2, or both CD4(+) T cells derived from human peripheral and cord blood were comparatively analyzed.

Suppressive role of C-terminal binding protein 1 in IL-4 synthesis in human T cells.

The functional role of C-terminal binding protein (CtBP)1, a transcriptional corepressor, in Th1 and Th2 cytokine expression in human T cells was investigated. Upon introduction of CtBP1 by lentiviral transduction system, IL-4 synthesis was suppressed but IFN-gamma was weakly up-regulated in human CD4(+) T cells. In contrast, a reduction of endogenously expressed CtBP1 in Jurkat T cells using RNAi technology selectively augmented IL-4 expression.

Downregulation of IL-13 gene transcription by T-bet in human T cells.

Background: Downregulation of a Th2 cytokine, IL-4, by a Th1-specific transcription factor, T-bet, has been demonstrated. However, the regulatory role of T-bet in another Th2 cytokine, IL-13, is not fully delineated.

Methods: IL-13 mRNA expression in Jurkat cells was examined by quantitative RT-PCR, while the transcriptional activity of 5'-flanking region in the IL-13 gene encompassing -1077 to +49 was investigated by fluorescence-based promoter reporter assay.

IL-4 gene transcription in human T cells is suppressed by T-bet.

Unlabelled: T-bet is crucially implicated in Th1 differentiation due to its strong promoting activity for IFN-gamma gene transcription. However, the regulatory role of T-bet in Th2 cytokines is not fully delineated.

Methods: The effect of T-bet on mRNA expression as well as the promoter activity of IL-4 in human T cells was investigated by employing quantitative RT-PCR and fluorescence-based promoter reporter assay procedures.