Osaka University

About: Osaka University is a education organization based out in Osaka, Japan. It is known for research contribution in the topics: Laser & Catalysis. The organization has 83778 authors who have published 185669 publications receiving 5158122 citations. The organization is also known as: Ōsaka daigaku.

IL-6 and NF-IL6 in acute-phase response and viral infection

Abstract: NF-IL6 was originally identified as a DNA-binding protein responsible for IL-1-stimulated IL-6 induction. Direct cloning of NF-IL6 revealed its homology with C/EBP. C/EBP is expressed in liver and adipose tissues and is supposed to regulate several hepatocyte- and adipocyte-specific genes. In contrast, NF-IL6 is suppressed in normal tissues, but is rapidly and drastically induced by LPS or inflammatory cytokines such as IL-1, TNF, and IL-6. NF-IL6 can also bind to the regulatory region of various genes including IL-8, G-CSF, IL-1 and immunoglobulin genes. Furthermore, NF-IL6 is shown to be identical to IL-6DBP, a DNA-binding protein responsible for IL-6-mediated induction in acute-phase proteins, demonstrating that NF-IL6 is responsible for the genes regulated by IL-6. These results indicate that NF-IL6 may be a pleiotropic mediator of many inducible genes involved in acute, immune, and inflammatory responses, like NFkB. In this regard, it is noteworthy that both an NF-IL6 binding site and an NFkB binding site are present in the inducible genes such as IL-6, IL-8, and several acute-phase genes. On the other hand, accumulating evidence has revealed that overproduction of IL-6 may be responsible for the pathogenesis and/or several symptoms of a variety of diseases, including autoimmune diseases, malignancies, and viral diseases. At present, the molecular mechanisms of abnormal expression of the IL-6 gene are not known. Recently it has become evident that interplays between viral proteins and cellular proteins play an important role in viral oncogenesis and infection. The fact that NF-IL6 binds to the enhancer core sequences of various viruses strongly suggests a possible relationship of virus infection and IL-6 expression. In fact some evidence (Mahe et al. 1991, Spergel et al. 1992) indicates that NF-IL6 may interact with viral gene enhancers or viral products, although there are no definite data about the involvement of NF-IL6 in viral pathogenesis. Future studies will be required to clarify whether or not the interplay between NF-IL6 and viral infection is responsible for deregulation of the IL-6 gene.

Regulatory T cells: recommendations to simplify the nomenclature

Abstract: c o rr e s p o n d e n c e npg © 2013 Nature America, Inc. All rights reserved. Regulatory T cells: recommendations to simplify the nomenclature To the Editor: Regulatory T cells (T reg cells) have attracted much interest from both basic and clinical immunologists. Although questions remain about their fundamental biology and their clinical potential has yet to be fully realized, considerable advances have been made in the under- standing of the differentiation, homeostasis and function of T reg cells. This new knowledge has led to a substantial increase in the number of Foxp3 + T reg cell subpopulations described in the literature and conse- quently to an increase in the use of new abbreviations and terminology. Furthermore, as the understanding of T reg cell biology has grown, so too has the realization that some aspects of the original terminology are no longer accurate, and its use has become less stringent. At the Third International Conference on Regulatory T Cells and Th Subsets and Clinical Application in Human Diseases held in Shanghai, China, on 13–16 October 2012, a small workshop was convened to discuss T reg cell nomenclature and to develop several recommendations. We hasten to add that this is simply a list of recommendations, and it remains the prerogative of journals to develop their own editorial preferences and for the authors to use the nomenclature they feel best suits their manuscript. However, we support the recommendations noted below. There were three general issues that provided the momentum for this workshop. First, the terms used for the principal Foxp3 + T reg cell populations—those that differentiate in the thymus, those that differ- entiate in the periphery and those generated in vitro—are not ideal, as these are, to some extent, inaccurate, ambiguous and/or uninformative. For example, the widely used term ‘natural T reg cell’ is misleading and ambiguous, as it indicates that all other Foxp3 + T reg cell populations are ‘unnatural’. It also does not convey any useful or accurate information. One feature of these Foxp3 + T reg cell populations that is more informa- tive is the anatomical location of their differentiation. Instead, use of the terms ‘thymus’, ‘periphery’ and ‘in vitro’ provides a clear indica- tion of whence the Foxp3 + T reg cells in question are derived. Thus, we would recommend that ‘natural Foxp3 + T reg cells’ instead be referred to as ‘thymus-derived T reg cells’ (Box 1). Consistent with the rationale above, we would recommend that Foxp3 + T reg cells that differentiate in the periphery be referred to as ‘peripherally derived T reg cells’ rather than ‘induced or adaptive T reg cells’ (Box 1). In this context, we noted that terms used to define a T reg cell subpopulation, such as ‘induced T reg cells’, are often used when the location of their differentiation is unclear. Thus, we would suggest that the newly recommended terms ‘thymus-derived T reg cells’ and ‘peripherally derived T reg cells’ be used only when the anatomical location of their differentiation has been clearly demonstrated. When the origin of the T reg cell being studied is unclear, the general term ‘Foxp3 + T reg cell’ would be more appropriate. Finally, to clearly distinguish between Foxp3 + T reg cell populations that are generated in vivo versus those generated in vitro, we would suggest nature immunology volume 14 number 4 april 2013 that the term ‘in vitro–induced T reg cells’ be used for all Foxp3 + T reg cell populations generated ex vivo, such as those generated through the use of transforming growth factor-b (Box 1). Second, there has been a growing tendency to use terms such as ‘T reg cells’ or ‘iT reg cells’ when confirmation of such identity is lacking. The frequent use of the term ‘T reg cells’ has been a particular problem in studies focusing on human T reg cells, as activated conventional T cells can also express Foxp3. The term ‘T reg cell’ should be used only when it is clear that the cells have (or had) suppressive ability or have a transcriptional, epigenetic and/or protein-expression signature that suggests that the cells in question are, beyond a reasonable doubt, Foxp3 + T reg cells (Box 1). Also, as indicated above, the terms ‘thymus- derived T reg cell’ and ‘peripherally derived T reg cells’ should be used only when the anatomical location of their development has been clearly demonstrated. Third, there has been progressive growth in the development and use of new T reg cell terminology that is likely to lead to more confusion and the further ‘jargonization’ of immunology. Until a new popula- tion has been extensively demonstrated to be unique, distinct from other populations and stable, we would recommend not coining new terms for such subpopulations (Box 1). Instead, we would encourage investigators to identify them through the use of prominent aspects of their expression pattern, such as a transcription factor or cytokine. Although the focus of this Correspondence has been CD4 + Foxp3 + T reg cell populations, many CD4 – Foxp3 – T reg cell populations have been described, and we would similarly recommend that new terms be used to describe these only when their identity and stability have been clearly defined. Box 1 T reg cell nomenclature recommendations 1. ‘Thymus-derived T reg cell (tT reg cell)’ should be used instead of ‘natural T reg cell (nT reg cell)’. 2. ‘Peripherally derived T reg cell (pT reg cell)’ should be used instead of ‘induced or adaptive T reg cell (iT reg cell or aT reg cell)’. 3. ‘In vitro–induced T reg cell (iT reg cell)’ should be used to clearly distinguish between those T reg cell populations generated in vivo versus those generated in vitro. 4. T reg cell terms should be used only when there is definitive evidence justifying their use. 5. The development and use of new T reg cell terminology should be limited, especially for subpopulations.

C66 fullerene encaging a scandium dimer

Abstract: The geometry of carbon cages (fullerenes) is governed by the isolated-pentagon rule (IPR)1,2, which states that the most stable fullerenes are those in which all pentagons are surrounded by five hexagons. Although this rule has been verified experimentally3,4,5, it is impossible for fullerenes in the range C60 to C70 to obey it. Here we describe the production and characterization of an IPR-violating metallofullerene, Sc2@C66, a C66 fullerene encaging a scandium dimer. Our results indicate that encapsulation of the metal dimer significantly stabilizes this otherwise extremely unstable C66 fullerene.

Aryl hydrocarbon receptor control of a disease tolerance defence pathway

Abstract: Disease tolerance is the ability of the host to reduce the effect of infection on host fitness. Analysis of disease tolerance pathways could provide new approaches for treating infections and other inflammatory diseases. Typically, an initial exposure to bacterial lipopolysaccharide (LPS) induces a state of refractoriness to further LPS challenge (endotoxin tolerance). We found that a first exposure of mice to LPS activated the ligand-operated transcription factor aryl hydrocarbon receptor (AhR) and the hepatic enzyme tryptophan 2,3-dioxygenase, which provided an activating ligand to the former, to downregulate early inflammatory gene expression. However, on LPS rechallenge, AhR engaged in long-term regulation of systemic inflammation only in the presence of indoleamine 2,3-dioxygenase 1 (IDO1). AhR-complex-associated Src kinase activity promoted IDO1 phosphorylation and signalling ability. The resulting endotoxin-tolerant state was found to protect mice against immunopathology in Gram-negative and Gram-positive infections, pointing to a role for AhR in contributing to host fitness.