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Medullary thymic epithelial cells (mTECs) are essential for thymic negative selection to prevent autoimmunity. Previous studies show that mTEC development is dependent on the signal transducers TRAF6 and NIK. However, the downstream target genes of signals controlled by these molecules remain unknown. We performed a microarray analysis on mRNAs(More)
Medullary thymic epithelial cells (mTECs) establish T cell self-tolerance through the expression of autoimmune regulator (Aire) and peripheral tissue-specific self-antigens. However, signals underlying mTEC development remain largely unclear. Here, we demonstrate crucial regulation of mTEC development by receptor activator of NF-kappaB (RANK) and CD40(More)
Medullary thymic epithelial cells (mTECs) expressing the autoimmune regulator AIRE and various tissue-specific antigens (TSAs) are critical for preventing the onset of autoimmunity and may attenuate tumor immunity. However, molecular mechanisms controlling mTEC development remain elusive. Here, we describe the roles of the transcription factor Spi-B in mTEC(More)
Regulatory T cells (Tregs), a subset of CD4(+) helper T cells, are crucial for immunological self-tolerance. Defect in development or function of Tregs results in autoimmune disease in human and mice. Whereas it is known that Tregs mainly develop in the thymus, the molecular mechanism underlying development of Treg is not fully understood. TRAF6-deficient(More)
Signal transduction pathways regulating NF-kappaB activation essential for microenvironment formation in secondary lymphoid organs remain to be determined. We investigated the effect of a deficiency of TNFR-associated factor 6 (TRAF6), which activates the classical NF-kappaB pathway, in splenic microenvironment formation. Two-week-old TRAF6-deficient mice(More)
Transcription factor NF-κB resides in the cytoplasm and translocates to the nucleus by application of extracellular stimuli. It is known that the nuclear NF-κB oscillates and different oscillation patterns lead to different gene expression. Nearly forty reports on modeling and simulation of nuclear NF-κB have been published to date. The computational models(More)
Modulation of the activity and content of cytochrome P-450 (CYP) in hepatic microsomes may be important to human health since these enzymes activate and inactivate a wide range of xenobiotics and food components. Regulation of the inducibility of most CYPs involves transcriptional regulation and post-transcriptional mRNA stabilization. We examined in the(More)
The transcription factor NF-κB shuttles between the cytoplasm and the nucleus, and nuclear NF-κB is known to oscillate with a cycle of 1.5-2.5 h following the application of external stimuli. Oscillation pattern of NF-κB is implicated in regulation of the gene expression profile. In a previous report, we found that the oscillation pattern of nuclear NF-κB(More)
Stress granules (SGs) are non-membranous cytoplasmic aggregates of mRNAs and related proteins, assembled in response to environmental stresses such as heat shock, hypoxia, endoplasmic reticulum (ER) stress, chemicals (e.g. arsenite), and viral infections. SGs are hypothesized as a loci of mRNA triage and/or maintenance of proper translation capacity ratio(More)
NF-κB is a transcription factor regulating expression of more than 500 genes, and its dysfunction leads to the autoimmune and inflammatory diseases. In malignant cancer cells, NF-κB is constitutively activated. Thus the elucidation of mechanisms for NF-κB regulation is important for the establishment of therapeutic treatment caused by incorrect NF-κB(More)