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Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly(More)
Negative frequency-dependent selection (NFDS) is one of the most powerful selective forces maintaining genetic polymorphisms in nature. Recently many prospective cases of polymorphisms by NFDS have been reported. Some of them are very complicated, although strongly supportive of the NFDS. Here we investigate NFDS in wild populations of the dimorphic(More)
Crohn's disease is a disorder of unknown etiology and complicated pathogenesis. A substantial amount of evidence has accumulated recently and has been applied to clinical practice. The present guidelines were developed based on recent evidence and the formal consensus of experts relevant to this disease. Here we provide an overview of these guidelines, as(More)
BACKGROUND Adalimumab is a fully human, monoclonal antibody against tumor necrosis factor that is approved in Western countries for the treatment of moderately to severely active ulcerative colitis (UC). METHODS This 52-week, phase 2/3, randomized, double-blind study evaluated adalimumab for induction and maintenance treatment in 273 anti-TNF-naive(More)
BACKGROUND Intraepithelial lymphocytes (IELs) in the intestine play important roles in the regulation of local immune responses. Although their functions have been studied in a variety of animal experiments, in vitro studies on spatiotemporal behaviors of IELs and their interaction with intestinal epithelial cells (IECs) have been hampered due to the lack(More)
We have demonstrated that intestinal epithelial cells produce interleukin 7 (IL-7), and IL-7 serves as a potent regulatory factor for proliferation of intestinal mucosal lymphocytes expressing functional IL-7 receptor. To clarify the mechanism by which locally produced IL-7 regulates the mucosal lymphocytes, we investigated IL-7 transgenic mice. Here we(More)
BACKGROUND Establishment of geographic morph frequency clines is difficult to explain in organisms with limited gene flow. Balancing selection, such as negative frequency-dependent selection (NFDS), is instead suggested to establish a morph frequency cline on a geographic scale at least theoretically. Here we tested whether a large-scale smooth cline in(More)
Intestinal epithelial cell-derived interleukin (IL)-7 functions as a pleiotropic and nonredundant cytokine in the human intestinal mucosa; however, the molecular basis of its production has remained totally unknown. We here showed that human intestinal epithelial cells both constitutively and when induced by gamma interferon (IFN-gamma) produced IL-7, while(More)
Inflammatory bowel diseases such as ulcerative colitis or Crohn's disease frequently cause epithelial damage in the intestine. In general, the intestinal epithelium is able to rapidly repair itself by the restitution, proliferation, and differentiation of epithelial cells when such tissue damage occurs. However, severe and continuous inflammation could(More)
Viral infections activate cellular expression of type I interferons (IFNs). These responses are partly triggered by RIG-I and mediated by Cardif, TBK1, IKKepsilon and IRF-3. This study analysed the mechanisms of dsRNA-induced IFN responses in various cell lines that supported subgenomic hepatitis C virus (HCV) replication. Transfection of dsRNA into Huh7,(More)