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Differentiation of naive CD4 T cells into type 2 helper (Th2) cells is accompanied by chromatin remodeling of Th2 cytokine gene loci. Hyperacetylation of histone H3 on nucleosomes associated with the interleukin (IL)-4, IL-13 and IL-5 genes was observed in developing Th2 cells but not in Th1 cells. Histone hyperacetylation on IL-5 gene-associated(More)
GATA3 expression is essential for type-2 helper T (Th2) cell differentiation. GATA3-mediated chromatin remodeling at the Th2 cytokine gene loci, including Th2-specific long range histone hyperacetylation of the interleukin (IL)-13/IL-4 gene loci, occurs in developing Th2 cells. However, little is known about the role of GATA3, if any, in the maintenance of(More)
The Polycomb group (PcG) gene products regulate the maintenance of the homeobox gene expression in Drosophila and vertebrates and also the cell cycle progression in thymocytes and Th2 cell differentiation in mature T cells. We herein studied the role of PcG gene bmi-1 product in Th1/Th2 cell differentiation and found that Bmi-1 facilitates Th2 cell(More)
There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduced expression of the receptor for this pathway has been(More)
Sox4 is a transcription factor that regulates various developmental processes. Here we show that Sox4 was induced by TGF-β and negatively regulated the transcription factor GATA-3, the master regulator of function of T helper type 2 (T(H)2) cells, by two distinct mechanisms. First, Sox4 bound directly to GATA-3, preventing its binding to GATA-3 consensus(More)
CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response(More)
Interleukin (IL)-4-induced STAT6 activation and the subsequent up-regulation of GATA3 are crucial for the induction of chromatin remodeling of the Th2 cytokine gene loci as Th2 cells undergo development. This study probes the role of these molecules in the maintenance of memory Th2 cells. IL-4 was not required to maintain the capability for Th2 cytokine(More)
IL-4 plays an important role in the induction of Th2 and Th9 cells, as well as in the inhibition of Th1 cell generation. We show that a combination of IL-4 and TGF-β augments the development of Th1 cells that express CD103 (CD103(+) Th1 cells) if IFN-γ is present. The T-box-containing transcription factor eomesodermin (Eomes) is preferentially expressed in(More)
The administration of concanavalin A (Con A) induces a rapid severe injury of hepatocytes in mice. Although the Con A-induced hepatitis is considered to be an experimental model of human autoimmune hepatitis, the precise cellular and molecular mechanisms that induce hepatocyte injury remain unclear. Here, we demonstrate that Valpha14 NKT cells are required(More)
In the periphery, upon antigen recognition by alphabetaTCR, naïve CD4 T cells undergo functional differentiation and acquire the ability to produce a specific set of cytokines. At least four Th cell subsets, i.e., Th1, Th2, Th17 and iTreg cells have so far been identified and the differentiation of each subset is driven by distinct cytokine sets. Antigen(More)