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.

Toll-like receptor 3 contributes to spinal glial activation and tactile allodynia after nerve injury.

Abstract: Toll-like receptors (TLRs) play an essential role in innate immune responses and in the initiation of adaptive immune responses. Microglia, the resident innate immune cells in the CNS, express TLRs. In this study, we show that TLR3 is crucial for spinal cord glial activation and tactile allodynia after peripheral nerve injury. Intrathecal administration of TLR3 antisense oligodeoxynucleotide suppressed nerve injury-induced tactile allodynia, and decreased the phosphorylation of p38 mitogen-activated protein kinase, but not extracellular signal-regulated protein kinases 1/2, in spinal glial cells. Antisense knockdown of TLR3 also attenuated the activation of spinal microglia, but not astrocytes, caused by nerve injury. Furthermore, down-regulation of TLR3 inhibited nerve injury-induced up-regulation of spinal pro-inflammatory cytokines, such as interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha. Conversely, intrathecal injection of the TLR3 agonist polyinosine-polycytidylic acid induced behavioral, morphological, and biochemical changes similar to those observed after nerve injury. Indeed, TLR3-deficient mice did not develop tactile allodynia after nerve injury or polyinosine-polycytidylic acid injection. Our results indicate that TLR3 has a substantial role in the activation of spinal glial cells and the development of tactile allodynia after nerve injury. Thus, blocking TLR3 in the spinal glial cells might provide a fruitful strategy for treating neuropathic pain.

Analysis of cytokine regulators inducing interferon production by mouse uterine natural killer cells.

Abstract: In mice and women, terminal differentiation of uterine natural killer (uNK) cells commences during endometrial decidualization. Both proliferation and interferon (IFN)-g are induced. Uterine NK cell precursors appear to home from secondary lymphoid organs to decidualizing uteri and localize mesometrially to the central decidua basalis, the site of maternal arterial modification at Gestation Days (gd) 9.5‐10. In mice, genetic absence of uNK cells results in absence of pregnancy-induced spiral artery modification. Administration of IFN-g to uNK-negative pregnant females induces arterial modifications without fetal loss. In this study, we investigated the roles of cytokines, known in other tissues to differentiate and activate NK cells, in induction of IFN-g production in normal mouse implantation sites. Fecundity evaluation, implantation site morphometry, and IFNg quantification in interleukin (IL)-12p400/0, IL-180/0, dual IL12p400/0/IL-180/0 and congenic strains revealed the importance of both IL-12 and IL-18 in the induction of spiral artery modification and IFN-g synthesis. Immediately after implantation, IL18 was localized transiently to decidual cells, but by gd8, IL-18 was produced solely by uNK cells, suggesting that early uNK cells are activated by stroma and lymphocyte-derived signals maintain later uNK cell activation. Mesometrial tissue of C57Bl/ 6J mice was examined by reverse transcription polymerase chain reaction assay in virgin, early postimplantation, and midgestation females for expression of the heterodimeric cytokines IL-23 (composed of IL-12p40 and a novel a chain), IL-27 (composed of two IL-12-related chains) and IL-27R. No expression was detected in virgin uteri. The four genes were induced by gd6, and uNK cells isolated from midgestation transcribed IL-23a and IL27R. This study advances the understanding of uNK cell activation during normal pregnancy. decidua, growth factors, immunology, pregnancy, uterus

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.