Shizuo Akira

Bio: Shizuo Akira is an academic researcher from Osaka University. The author has contributed to research in topics: Innate immune system & Immune system. The author has an hindex of 261, co-authored 1308 publications receiving 320561 citations. Previous affiliations of Shizuo Akira include University of California, Berkeley & Wakayama Medical University.

Abrogation of Bronchial Eosinophilic Inflammation and Airway Hyperreactivity in Signal Transducers and Activators of Transcription (STAT)6-deficient Mice

Abstract: Signal transducers and activators of transcription 6 (STAT6) is essential for interleukin 4–mediated responses, including class switching to IgE and induction of type 2 T helper cells. To investigate the role of STAT6 in allergic asthma in vivo, we developed a murine model of allergen-induced airway inflammation. Repeated exposure of actively immunized C57BL/6 mice to ovalbumin (OVA) aerosol increased the level of serum IgE, the number of eosinophils in bronchoalveolar lavage (BAL) fluid, and airway reactivity. Histological analysis revealed peribronchial inflammation with pulmonary eosinophilia in OVA-treated mice. In STAT6-deficient (STAT6−/−) C57BL/6 mice treated in the same fashion, there were no eosinophilia in BAL and significantly less peribronchial inflammation than in wild-type mice. Moreover STAT6−/− mice had much less airway reactivity than wild-type mice. These findings suggest that STAT6 plays a crucial role in the pathogenesis of allergen-induced airway inflammation.

A Subset of Toll-Like Receptor Ligands Induces Cross-presentation by Bone Marrow-Derived Dendritic Cells

Abstract: Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8(+) CTLs. Detection of microbial products by Toll-like receptors (TLRs) leads to activation of DCs and subsequent orchestration of an adaptive immune response. We hypothesized that microbial TLR ligands could activate DCs to cross-present Ag to CTLs. Using DCs and CTLs in an in vitro cross-presentation system, we show that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast to presentation of Ag to CD4(+) T cells by immature DCs, TLR-induced cross-presentation is mediated by mature DCs, is independent of endosomal acidification, and relies on cytosolic Ag processing machinery.

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia

Abstract: T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a poor prognosis and no available targeted therapies; now two histone H3 lysine 27 demethylases, JMJD3 and UTX, are shown to have contrasting roles in human T-ALL cells and a mouse model of the disease, and a small molecule demethylase inhibitor is found to inhibit the growth of T-ALL cell lines, introducing a potential therapeutic avenue for acute leukaemia. Two histone H3 lysine 27 demethylases, JMJD3 and UTX, are shown here to have contrasting roles in human T-cell acute lymphoblastic leukaemia (T-ALL) cells and a mouse model of the disease. JMJD3 is overexpressed in T-ALL and essential for initiation and maintenance of disease, whereas UTX is a target of inactivating mutations in human T-ALL and acts a tumour suppressor. A small-molecule demethylase inhibitor inhibits the growth of T-ALL cell lines, introducing a potential therapeutic avenue for an acute leukemia that has a poor prognosis and no currently available targeted therapies. T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a dismal overall prognosis, including a relapse rate of up to 25%, mainly because of the lack of non-cytotoxic targeted therapy options. Drugs that target the function of key epigenetic factors have been approved in the context of haematopoietic disorders1, and mutations that affect chromatin modulators in a variety of leukaemias have recently been identified2,3; however, ‘epigenetic’ drugs are not currently used for T-ALL treatment. Recently, we described that the polycomb repressive complex 2 (PRC2) has a tumour-suppressor role in T-ALL4. Here we delineated the role of the histone 3 lysine 27 (H3K27) demethylases JMJD3 and UTX in T-ALL. We show that JMJD3 is essential for the initiation and maintenance of T-ALL, as it controls important oncogenic gene targets by modulating H3K27 methylation. By contrast, we found that UTX functions as a tumour suppressor and is frequently genetically inactivated in T-ALL. Moreover, we demonstrated that the small molecule inhibitor GSKJ4 (ref. 5) affects T-ALL growth, by targeting JMJD3 activity. These findings show that two proteins with a similar enzymatic function can have opposing roles in the context of the same disease, paving the way for treating haematopoietic malignancies with a new category of epigenetic inhibitors.

Regulation of Dendritic Cell Function Through Toll-like Receptors

Abstract: Higher animals establish host defense by orchestrating innate and adaptive immunity. This is mediated by professional antigen presenting cells, i.e. dendritic cells (DCs). DCs can incorporate pathogens, produce a variety of cytokines, maturate, and present pathogen-derived peptides to T cells, thereby inducing T cell activation and differentiation. These responses are triggered by microbial recognition through type I transmembrane proteins, Toll-like receptors (TLRs) on DCs. TLRs consist of ten members and each TLR is involved in recognizing a variety of microorganism-derived molecular structures. TLR ligands include cell wall components, proteins, nucleic acids, and synthetic chemical compounds, all of which can activate DCs as immune adjuvants.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.

Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

Cancer-related inflammation.

Abstract: The mediators and cellular effectors of inflammation are important constituents of the local environment of tumours. In some types of cancer, inflammatory conditions are present before a malignant change occurs. Conversely, in other types of cancer, an oncogenic change induces an inflammatory microenvironment that promotes the development of tumours. Regardless of its origin, 'smouldering' inflammation in the tumour microenvironment has many tumour-promoting effects. It aids in the proliferation and survival of malignant cells, promotes angiogenesis and metastasis, subverts adaptive immune responses, and alters responses to hormones and chemotherapeutic agents. The molecular pathways of this cancer-related inflammation are now being unravelled, resulting in the identification of new target molecules that could lead to improved diagnosis and treatment.