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.

IL-1α Modulates Neutrophil Recruitment in Chronic Inflammation Induced by Hydrocarbon Oil

Abstract: Exposure to naturally occurring hydrocarbon oils is associated with the development of chronic inflammation and a wide spectrum of pathological findings in humans and animal models. The mechanism underlying the unremitting inflammatory response to hydrocarbons remains largely unclear. The medium-length alkane 2,6,10,14 tetramethylpentadecane (also known as pristane) is a hydrocarbon that potently elicits chronic peritonitis characterized by persistent infiltration of neutrophils and monocytes. In this study, we reveal the essential role of IL-1α in sustaining the chronic recruitment of neutrophils following 2,6,10,14 tetramethylpentadecane treatment. IL-1α and IL-1R signaling promote the migration of neutrophils to the peritoneal cavity in a CXCR2-dependent manner. This mechanism is at least partially dependent on the production of the neutrophil chemoattractant CXCL5. Moreover, although chronic infiltration of inflammatory monocytes is dependent on a different pathway requiring TLR-7, type I IFN receptor, and CCR2, the adaptor molecules MyD88, IL-1R-associated kinase (IRAK)-4, IRAK-1, and IRAK-2 are shared in regulating the recruitment of both monocytes and neutrophils. Taken together, our findings uncover an IL-1α-dependent mechanism of neutrophil recruitment in hydrocarbon-induced peritonitis and illustrate the interactions of innate immune pathways in chronic inflammation.

Biological and clinical aspects of

Abstract: 33 Tony, H-P., Phillips, N.E. and Parker, E..C. (1985)J. Exp. Med. 162, 1695 1708 34 Kupfer, A. and Singer, S.J. (1989) J. Exp. Med. 170, 1697--1713 35 Watanabe, M., Wegma, D.R., Ochi, A. and Hozumi, N. (1986) Proc. Natl Acad. Sci. USA 83, 5247 5251 36 Bonnefoy, J.Y., Guillot, O., Spits, H. etal. (1988) J. Exp. Med. 167, 57 72 37 Lee, W.T., Rao, M and Conrad, D.H (1987) ./. Immunoi 139,1191 1198 38 MacLennan, I.C.M. and Gray, D. (1936)Immunol. Rev. 91, 61 85 39 Liu, Y-J., Joshua, D.E., Williams, G.T. et al. (1989)Nature 342,929 931 40 Reynes, M., Aubert, J-P., Cohen, J.H.M. etal. (1985) J. Imrnunol. 135, 2687 2694 41 Johnson, G.D., MacLennan, I.C.M., Ling, N.R. and Hardie, L. (1987)in Leukocyte I-yping III (McM0chael, A.J. et al., eds). p. 387, Oxford University Press 42 Sellheyer, K., <"~ .... ;"~ -," ~;J9 R. and Steln, 11. (1989) C/in £xp Immunol. 78, 431 436 43 Swendeman, S. and 1-horley Lawson, D A (1987) EMBO J 6,1637 1642 44 Gordon, J., Cairns, J.A, Millsum, M.J., Gillb, S. and Guy, G.R. (1988) Eur. 2. Irnmunol. 18, 156! 1565 45 Uchibayashi, N, Kikutani, H., Barsumian. E_L. et al (1989) J. Immunol. 142, 3901 3908 46 Fanger, M.W., Shen, L., Ora,iano, R.F. and Guyre, P.M (1989) Immunol. Today 1 O, 92 99 47 Kikutani, H., Invi, S., Sato, R. etal. (1986) Ce1147, 651 665 48 Phillips, N.E. and Parker, D C (1984)J. Immunol. 132, 627 632 49 Miettinen, H.M., Rose, JK ar,4 Mellman, I (1989) Cell 58, 317 327

Id2-, RORγt-, and LTβR-independent initiation of lymphoid organogenesis in ocular immunity

Abstract: The eye is protected by the ocular immunosurveillance system. We show that tear duct-associated lymphoid tissue (TALT) is located in the mouse lacrimal sac and shares immunological characteristics with mucosa-associated lymphoid tissues (MALTs), including the presence of M cells and immunocompetent cells for antigen uptake and subsequent generation of mucosal immune responses against ocularly encountered antigens and bacteria such as Pseudomonas aeruginosa. Initiation of TALT genesis began postnatally; it occurred even in germ-free conditions and was independent of signaling through organogenesis regulators, including inhibitor of DNA binding/differentiation 2, retinoic acid-related orphan receptor gammat, lymphotoxin (LT) alpha1beta2-LTbetaR, and lymphoid chemokines (CCL19, CCL21, and CXCL13). Thus, TALT shares immunological features with MALT but has a distinct tissue genesis mechanism and plays a key role in ocular immunity.

Viral 5'-triphosphate RNA and non-CpG DNA aggravate autoimmunity and lupus nephritis via distinct TLR-independent immune responses

Abstract: Certain viral nucleic acids aggravate autoimmunity through nucleic acid-specific TLR. Viral 5'-triphosphate RNA (3P-RNA) and double-stranded non-CpG DNA induce antiviral immunity via TLR-independent pathways but their role in autoimmunity is unknown. Transient exposure of 16-wk-old MRL(lpr/lpr) mice to 3P-RNA aggravated lupus nephritis by increasing IFN signaling and decreasing CD4(+)CD25(+) T cells. By contrast, transient exposure to non-CpG DNA exacerbate lupus nephritis in association with splenomegaly, lymphoproliferation, hypergammaglobulinaemia and increased B220(+)CD138(+) plasma cells. Both, 3P-RNA and non-CpG DNA increased glomerular complement factor C3c deposits but both nucleic acid formats were less potent in aggravating renal pathology as compared with CpG DNA. 3P-RNA and non-CpG DNA also localized to the glomerular mesangial cells and activated cultured mesangial cells to produce IL-6. We conclude, 3P-RNA or non-CpG DNA both trigger autoimmune disease in MRL(lpr/lpr) mice by specifically activating adaptive immunity but similarly enhance inflammation on the tissue level.

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.