九州大学 · 免疫学・微生物学
Shinya Tanaka教授の研究室は、神経発生と免疫調節の分子メカニズムに焦点を当てており、特に神経前駆細胞の決定を制御する転写因子ネットワークや、自己免疫疾患の発症に関与するT細胞・B細胞の機能制御機構を解明しています。神経線維形成関連転写因子(SOX1/2/3、Nestin)の調節機構や、Th17細胞やTfh細胞の発生・機能制御、ならびに自己抗体産生の抑制を担うB細胞アナジーの破綻機構を分子レベルで解明しています。これらの研究は、神経疾患や自己免疫疾患の病態解明および治療戦略の開発に貢献しています。
Figures are computed from collected data and may differ slightly.
Intermediate-filament Nestin and group B1 SOX transcription factors (SOX1/2/3) are often employed as markers for neural primordium, suggesting their regulatory link. We have identified adjacent and essential SOX and POU factor binding sites in the Nestin neural enhancer. The 30-bp sequence of the enhancer including these sites (Nes30) showed a nervous system-specific and SOX-POU-dependent enhancer activity in multimeric forms in transfection assays and was utilized in assessing the specificity o
Summary This study examines high-dimensional forecasting and variable selection via folded-concave penalized regressions. The penalized regression approach leads to sparse estimates of the regression coefficients and allows the dimensionality of the model to be much larger than the sample size. First, we discuss the theoretical aspects of a penalized regression in a time series setting. Specifically, we show the oracle inequality with ultra-high-dimensional time-dependent regressors. Then we sho
Effector Th17 cells are a major source of IL-17, a critical inflammatory cytokine in autoimmune diseases and in host defenses during bacterial infections. Recently, splenic lymphoid tissue inducer-like cells have been reported to be a source of T cell independent IL-17. In this study, we report that the immune system contains a unique set of natural occurring IL-17 producing cell, "natural" Th17 (nTh17), which are a memory-like T cell subset. The nTh17 cells can develop in the absence of the IL-
Transforming growth factor-β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo<i>.</i> Trim33 was required for induction in vitro of Th17, but not T r
Humoral immunity, including Ab switching and somatic hypermutation, is critically regulated by CD4(+) T cells. T follicular helper (Tfh) cells have been recently shown to be a distinct T cell subset important in germinal center reactions. The transcriptional regulation of Tfh cell development and function has not been well understood. In this study, we report that C/EBPα, a basic region/leucine zipper transcription factor, is highly expressed in Tfh cells. Cebpa-deficient CD4(+) T cells exhibit
B cell anergy plays a critical role in maintaining self-tolerance by inhibiting autoreactive B cell activation to prevent autoimmune diseases. Here, we demonstrated that Fc receptor-like 5 (Fcrl5) upregulation contributes to autoimmune disease pathogenesis by disrupting B cell anergy. Fcrl5-a gene whose homologs are associated with human autoimmune diseases-is highly expressed in age/autoimmunity-associated B cells (ABCs), an autoreactive B cell subset. By generating B cell-specific Fcrl5 transg
Despite the existence of central tolerance mechanisms, including clonal deletion and receptor editing to eliminate self-reactive B cells, moderately self-reactive cells still survive in the periphery (about 20% of peripheral B cells). These cells normally exist in a functionally silenced state called anergy; thus, anergy has been thought to contribute to tolerance by active-silencing of potentially dangerous B cells. However, a positive rationale for the existence of these anergic B cells has re
A human friendly man-machine interface is important to realize mobile robots which have a close relation with people. This paper proposes a method to operate a mobile robot by gesture recognition. Hand gestures are utilized as natural operations for a person. A hand's region is extracted from a sequence of images using color information, and gesture recognition is realized by DP matching for a sequence of features of hand's regions. So as to realize robustness, a face's area is utilized to estim
Gene expression must be strictly controlled during cell differentiation and function in mammalian systems. DNA methylation plays an important role in this process, and its pattern is shaped by balancing the activity of methyltransferases and demethylases. Ten-eleven translocation (TET) was identified as a demethylase that catalyzes the oxidation reaction of the methyl group of 5-methylcytosine (5mC), converting it to 5-hydroxymethylcytosine (5hmC). Recently, indispensable roles of TET proteins i
B cell initial activity is regulated through a balance of activation and suppression mediated by regulatory molecules expressed in B cells; however, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the function of the Fc receptor-like (Fcrl) family molecule Fcrl5, which is constitutively expressed in naive B cells, in humoral immune responses. Our study demonstrated that B cell-specific overexpression of Fcrl5 enhanced antibody (Ab)
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