The Runx1 Transcription Factor Inhibits the Differentiation of Naive CD4+ T Cells into the Th2 Lineage by Repressing GATA3 Expression

Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation

ETS-VIIIを利用した災害医療支援のための立体画像伝送の研究

It is pointed out that a lot of people are dead or injured, and the functions of the infrastructure are lost such as the cellular phone, the gas , water service, electricity, and roads, when the communication network system on the ground is broken down by wide-scale disaster. In order to overcome such inconvenient conditions, the construction of Tel-Radiology system not depending on the situations of the ground should be established rapidly. In addition, if 3D image technology is applied for Tel-Radiology, it may lead to the contribution of the triage to the efficiently improved operations in several areas. In this paper, we studied the capability of 3D image technology applying to Tel-Radiology. As a result of sufficient investment of bit stream data transmission of stereo 3D moving pictures employed the ETS-VIII satellite , it is found that the proposed system function well in the experiment assuming a telemedicine.

The Transcription Factor GATA3 Actively Represses RUNX3 Protein-Regulated Production of Interferon-γ

SummaryThe transcription factor GATA3 is crucial for the differentiation of naive CD4+ T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-γ (IFN-γ)-producing cells in the absence of interleukin-12 (IL-12) and IFN-γ. Such IFN-γ production was transcription factor T-bet independent. Another T-box-containing transcription factor Eomes, but not T-bet, was induced both in GATA3-deficient CD4+ T cells differentiated under Th2 cell conditions and in Th2 cells with enforced Runx3 expression, contributing to IFN-γ production. GATA3 overexpression blocked Runx3-mediated Eomes induction and IFN-γ production, and GATA3 protein physically interacted with Runx3 protein. Furthermore, we found that Runx3 directly bound to multiple regulatory elements of the Ifng gene and that blocking Runx3 function in either Th1 or GATA3-deficient “Th2” cells results in diminished IFN-γ production by these cells. Thus, the Runx3-mediated pathway, actively suppressed by GATA3, induces IFN-γ production in a STAT4- and T-bet-independent manner

B-Site Deficiencies in A -site-Ordered Perovskite LaCu3Pt3.75O12\mathrm{LaCu_3Pt_{3.75}O_{12}}

An A-site-ordered perovskite $LaCu_{3}Pt_{3.75}O_{12}$ was synthesized by replacing $Ca^{2+}$ with $La^{3+}$ in a cubic quadruple $AA′_{3}B_{4}O_{12}-type$ perovskite $CaCu_{3}Pt_{4}O_{12}$ under high-pressure and high-temperature of 15 GPa and 1100 $^\circ C$. In $LaCu_{3}Pt_{3.75}O_{12}$, 1/16 of B-site cations are vacant to achieve charge balance. The $\mathit{B}$-site deficiencies were evidenced by crystal structure refinement using synchrotron X-ray powder diffraction, hard X-ray photoemission spectroscopy, and soft X-ray absorption spectroscopy, leading to the ionic model $La^{3}+Cu^{2}+_{3}Pt^{4+}$$_{3.75}O^{2–}$$_{12}$. Magnetic susceptibility data for this compound indicated a spin-glass-like behavior below $T_{g}$ = 3.7 K, which is attributed to disturbance of the antiferromagnetic superexchange interaction by the $\mathit{B}$-site deficiencies

IL-7Rα expression regulates murine dendritic cell sensitivity to thymic stromal lymphopoietin

Thymic stromal lymphopoietin (TSLP) and IL-7 are related cytokines that mediate growth and differentiation events in the immune system. They signal through IL-7Rα–containing receptors. Target cells of TSLP in Th2 responses include CD4 T cells and dendritic cells (DCs). Although it has been reported that expression of TSLP receptor (TSLPR) on CD4 T cells is required for OVA-induced lung inflammation, DCs have also been shown to be target cells of TSLP. In this study, we show that murine ex vivo splenic DCs are unresponsive to TSLP, as they fail to phosphorylate STAT5, but in vitro overnight culture, especially in presence of IL-4, renders DCs responsive to both TSLP and IL-7. This induced responsiveness is accompanied by dramatic upregulation of IL-7Rα on DCs with little change in expression of TSLPR or of γc. In splenic DCs, the induction of IL-7Rα occurs mainly in CD8− DCs. In vivo, we found that IL-4 has a differential regulatory role on expression of IL-7Rα depending on the cell type; IL-4 decreases IL-7Rα expression on CD4 T cells whereas it upregulates the expression on DCs. Our results indicate that the induction of IL-7Rα expression on DCs is critical for TSLP responsiveness and that IL-4 can upregulate IL-7Rα on DCs

Histone demethylases UTX and JMJD3 are required for NKT cell development in mice

Abstract Background Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells. Results We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected. Loss of NKT cells is cell intrinsic and not due to an insufficient selection environment. The absence of NKT cells in UTX/JMJD3-deficient mice protects mice from concanavalin A‐induced liver injury, a model of NKT‐mediated hepatitis. GO‐analysis of RNA-seq data indicates that cell cycle genes are downregulated in UTX/JMJD3-deleted NKT progenitors, and suggest that failed expansion may account for some of the cellular deficiency. The phenotype appears to be demethylase‐dependent, because UTY, a homolog of UTX that lacks catalytic function, is not sufficient to restore their development and removal of H3K27me3 by deletion of EZH2 partially rescues the defect. Conclusions NKT cell development and gene expression is sensitive to proper regulation of H3K27 methylation. The H3K27me3 demethylase enzymes, in particular UTX, promote NKT cell development, and are required for effective NKT function