研究実績(2011～2015年)

Inada M, Takita M, Yokoyama S, Watanabe K, Tominari T, Matsumoto C, Hirata M, Maru Y, Maruyama T, Sugimoto Y, Narumiya S, Uematsu S, Akira S, Murphy G, Nagase H, Miyaura C.Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling that Drives Tumor Growth, Angiogenesis and Metastasis. J Biol Chem. 2015 Oct 16. pii: jbc.M115.669481. [Epub ahead of print]

Matsuda H, Hosono K, Tsuru S, Kurashige C, Sekiguchi K, Akira S, Uematsu S, Okamoto H, Majima M.Roles of mPGES-1, an inducible prostaglandin E synthase, in enhancement of LPS-induced lymphangiogenesis in a mouse peritonitis model.Life Sci. 2015 Dec 1;142:1-7. doi: 10.1016/j.lfs.2015.10.008.

Flores-Langarica A, Bobat S, Marshall JL, Yam-Puc JC, Cook CN, Serre K, Kingsley RA, Flores-Romo L, Uematsu S, Akira S, Henderson IR, Toellner KM, Cunningham AF. Soluble flagellin co-immunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production. Eur J Immunol. 2015 Jun 2. doi: 10.1002/eji.201545564. [Epub ahead of print]

Maruyama K, Fukasaka M, Uematsu S, Takeuchi O, Kondo T, Saitoh T, Martino M, Akira S. 5-azacytidine-induced protein 2 (AZI2) regulates bone mass by fine-tuning osteoclast survival. J Biol Chem. J Biol Chem. 2015 Apr 10;290(15):9377-86. doi: 10.1074/jbc.M114.631374.

Atif SM, Lee SJ, Li LX, Uematsu S, Akira S, Gorjestani S, Lin X, Schweighoffer E, Tybulewicz VL, McSorley SJ.

Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9. Eur J Immunol. 2014 Nov 27. doi: 10.1002/eji.201444744.

Goto Y, Obata T, Kunisawa J, Sato S, Ivanov II, Lamichhane A, Takeyama N, Kamioka M, Sakamoto M, Matsuki T, Setoyama H, Imaoka A, Uematsu S, Akira S, Domino SE, Kulig P, Becher B, Renauld JC, Sasakawa C, Umesaki Y, Benno Y, Kiyono H. Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science. 2014 Sep 12;345(6202):1254009. doi:10.1126/science.1254009.

Reynolds LA, Harcus Y, Smith KA, Webb LM, Hewitson JP, Ross EA, Brown S, Uematsu S, Akira S, Gray D, Gray M, MacDonald AS, Cunningham AF, Maizels RM. MyD88 Signaling Inhibits Protective Immunity to the Gastrointestinal Helminth Parasite Heligmosomoides polygyrus. J Immunol.2014 Sep 15;193(6):2984-93. doi: 10.4049/jimmunol.1401056.

Takemura N, Kawasaki T, Kunisawa J, Sato S, Lamichhane A, Kobiyama K, Aoshi T, Ito J, Mizuguchi K, Karuppuchamy T, Matsunaga K, Miyatake S, Mori N, Tsujimura T, Satoh T, Kumagai Y, Kawai T, Standley DM, Ishii KJ, Kiyono H, Akira S, Uematsu S. Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Nat Commun. 2014 Mar 18;5:3492. doi: 10.1038/ncomms4492.

Schülke S, Wolfheimer S, Gadermaier G, Wangorsch A, Siebeneicher S, Briza P, Spreitzer I, Schiller D, Loeschner B, Uematsu S, Ryffel B, Akira S, Waibler Z, Vieths S, Toda M, Scheurer S. Prevention of Intestinal Allergy in Mice by rflaA:Ova Is Associated with Enforced Antigen Processing and TLR5-Dependent IL-10 Secretion by mDC. PLoS One.2014 Feb 7;9(2):e87822.

Atif SM, Uematsu S, Akira S, McSorley SJ. CD103-CD11b+ dendritic cells regulate the sensitivity of CD4 T-cell responses to bacterial flagellin. Mucosal Immunol. 2014 Jan;7(1):68-77.

Cording S, Fleissner D, Heimesaat MM, Bereswill S, Loddenkemper C, Uematsu S, Akira S, Hamann A, Huehn J. Commensal microbiota drive proliferation of conventinal and Foxp3+ regulatory CD4+ T cells in mesenteric lymph nodes and Peyer's patches. Eur J Microbiol Immunol (Bp). 2013 Mar;3(1):1-10. Epub 2013 Mar 13.

Sugita K, Ikenouchi-Sugita A, Nakayama Y, Yoshioka H, Nomura T, Sakabe J, Nakahigashi K, Kuroda E, Uematsu S, Nakamura J, Akira S, Nakamura M, Narumiya S, Miyachi Y, Tokura Y, Kabashima K.Prosyaglandin E2 is critical for the development of niacin-deficiency-induced photosensitivity via ROS production. Sci Rep. 2013 Oct 17;3:2973. doi: 10.1038/srep02973.

Ogino T, Nishimura J, Barman S, Kayama H, Uematsu S,Okuzaki D, Osawa H, Haraguchi N, Uemura M, Hata T, Takemasa I, Mizushima T, Yamamoto H, Takeda K, Doki Y, Mori M.Increased Th17-Inducing Activity of CD14+ CD163low Myeloid Cells in Intestinal Lamina Propria of Patients with Crohn's Disease. Gastroenterology. 2013 Aug 29. doi:pii: S0016-5085(13)01269-9. 10.1053/j.gastro.2013.08.049. [Epub ahead of print]

Maruyama K, Uematsu S, Kondo T, Takeuchi O, Martino MM, Kawasaki T, Akira S.Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP.J Exp Med. 210(10):1947-60, 2013.

Nguyen TC, Hong SH, Sin JI, Vu HV, Jeong K, Cho KO, Uematsu S, Akira S, Lee SE, Rhee JH.Flagellin enhances tumor-specific CD8+ T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model.Vaccine. 20;31(37):3879-87, 2013.

Kawashima T, Kosaka A, Yan H, Guo Z, Uchiyama R, Fukui R, Kaneko D, Kumagai Y, You DJ, Carreras J Uematsu S,Jang MH, Takeuchi O, Kaisho T, Akira S, Miyake K, Tsutsui H, Saito T, Nishimura I, Tsuji NM.Double-Stranded RNA of Intestinal Commensal but Not Pathogenic Bacteria Triggers Production of Protective Interferon-β.Immunity. 38(6):1187-97, 2013.

Fukasaka M, Ori D, Kawagoe T, Uematsu S, Maruyama K, Okazaki T, Kozaki T, Imamura T, Tartey S, Mino T, Satoh T, Akira S, Takeuchi O. Critical Role of AZI2 in GM-CSF-Induced Dendritic Cell Differentiation. J Immunol. 190(11):5702-11, 2013.

Kaiko GE, Loh Z, Spann K, Lynch JP, Lalwani A, Zheng Z, Davidson S,Uematsu S,Akira S, Hayball J, Diener KR, Baines KJ, Simpson JL, Foster PS, Phipps S. Toll-like receptor 7 gene deficiency and early-life Pneumovirus infection interact to predispose toward the development of asthma-like pathology in mice. J Allergy Clin Immunol. 131(5):1331-1339, 2013.

Akitake Y, Nakatani Y, Kamei D, Hosokawa M, Akatsu H, Uematsu S, Akira S, Kudo I, Hara S, Takahashi M. Microsomal prostaglandin E synthase-1 is induced in alzheimer's disease and its deletion mitigates alzheimer's disease-like pathology in a mouse model. J Neurosci Res. 91(7):909-19, 2013.

Fujiwara N, Porcelli SA, Naka T, Yano I, Maeda S, Kuwata H, Akira S,Uematsu S, Takii T, Ogura H, Kobayashi K. Bacterial sphingophospholipids containing non-hydroxy fatty acid activate murine macrophages via Toll-like receptor 4 and stimulate bacterial clearance. Biochim Biophys Acta. 1831(6):1177-1184, 2013.

Takeuchi C, Matsumoto Y, Kohyama K,Uematsu S, Akira S, Yamagata K, Takemiya T. Microsomal prostaglandin E synthase-1 aggravates inflammation and demyelination in a mouse model of multiple sclerosis. Neurochem Int. 62(3):271-80, 2013.

Flores-Langarica A, Marshall JL, Hitchcock J, Cook C, Jobanputra J, Bobat S, Ross EA, Coughlan RE, Henderson IR, Uematsu S, Akira S, Cunningham AF. Systemic Flagellin Immunization Stimulates Mucosal CD103+ Dendritic Cells and Drives Foxp3+ Regulatory T Cell and IgA Responses in the Mesenteric Lymph Node. J Immunol. 189(12):5745-54, 2012.

Shibata T, Takemura N, Motoi Y, Goto Y, Karuppuchamy T, Izawa K, Li X, Akashi-Takamura S, Tanimura N, Kunisawa J, Kiyono H, Akira S, Kitamura T, Kitaura J, Uematsu S, Miyake K. PRAT4A-dependent expression of cell surface TLR5 on neutrophils, classical monocytes and dendritic cells. Int Immunol. 189(12):5745-54, 2012.

Kreutz M, Giquel B, Hu Q, Abuknesha R, Uematsu S, Akira S, Nestle FO, Diebold SS. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity. PLoS One. 7(7):e40208, 2012.

Kuroki Y, Sasaki Y, Kamei D, Akitake Y, Takahashi M, Uematsu S, Akira S, Nakatani Y, Kudo I, Hara S. Deletion of microsomal prostaglandin E synthase-1 protects neuronal cells from cytotoxic effects of β-amyloid peptide fragment 31-35. Biochem Biophys Res Commun. 424(3):409-13, 2012.

Chucair-Elliott AJ, Elliott MH, Wang J, Moiseyev GP, Ma JX, Politi LE, Rotstein NP, Akira S, Uematsu S, Ash JD. Leukemia Inhibitory Factor Coordinates the Down-regulation of the Visual Cycle in the Retina and Retinal-pigmented Epithelium. J Biol Chem. 287(29):24092-102, 2012.

Yoshioka W, Aida-Yasuoka K, Fujisawa N, Kawaguchi T, Ohsako S, Hara S, Uematsu S, Akira S, Tohyama C. Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice. Toxicol Sci. 127(2):547-54, 2012.

Sasaki Y, Kamei D, Ishikawa Y, Ishii T, Uematsu S, Akira S, Murakami M, Hara S. Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis. Oncogene. 31(24):2943-52, 2012.

Moreira AP, Cavassani KA, Ismailoglu UB, Hullinger R, Dunleavy MP, Knight DA, Kunkel SL, Uematsu S, Akira S, Hogaboam CM. The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A. J Clin Invest. 121(11): 4420-32, 2011.

Fujimoto K, Karuppuchamy T, Takemura N, Shimohigoshi M, Machida T, Haseda Y, Aoshi T, Ishii KJ, Akira S, Uematsu S*. A new subset of CD103+CD8a+ DCs in the small intestine express TLR3, TLR7 and TLR9, and induce Th1 response and CTL activity. J Immunol. 186(11):6287-95, 2011. (*Corresponding author).

Kuroda E, Ishii KJ, Uematsu S, Ohata K, Coban C, Akira S, Aritake K, Urade Y, Morimoto Y. Silica Crystals and Aluminum Salts Regulate the Production of Prostaglandin in Macrophages via NALP3 Inflammasome-Independent Mechanisms. Immunity. 34(4):514-26, 2011.

Davidson S, Kaiko G, Loh Z, Lalwani A, Zhang V, Spann K, Foo SY, Hansbro N, Uematsu S, Akira S, Matthaei KI, Rosenberg HF, Foster PS, Phipps S. Plasmacytoid Dendritic Cells Promote Host Defense against Acute Pneumovirus Infection via the TLR7-MyD88-Dependent Signaling Pathway. J Immunol. 186(10):5938-48, 2011.

Letran SE, Lee SJ, Atif SM, Flores-Langarica A, Uematsu S, Akira S, Cunningham AF, McSorley SJ. TLR5-Deficient Mice Lack Basal Inflammatory and Metabolic Defects but Exhibit Impaired CD4 T Cell Responses to a Flagellated Pathogen. J Immunol. 186(9):5406-12, 2011.

Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, Akira S. Antiviral protein Viperin promotes Toll-like receptor 7- and Toll-like receptor 9-mediated type I interferon production in plasmacytoid dendritic cells. Immunity. 34(3):352-63, 2011.

Seo SU, Kwon HJ, Ko HJ, Byun YH, Seong BL, Uematsu S, Akira S, Kweon MN. Type I interferon signaling regulates Ly6C(hi) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog. 7(2):e1001304, 2011.

Isono M, Suzuki T, Hosono K, Hayashi I, Sakagami H, Uematsu S, Akira S, DeClerck YA, Okamoto H, Majima M. Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice. Life Sci. 88(15-16):693-700, 2011.

Lousberg EL, Diener KR, Fraser CK, Phipps S, Foster PS, Chen W, Uematsu S, Akira S, Robertson SA, Brown MP, Hayball JD. Antigen-specific T-cell responses to a recombinant fowlpox virus are dependent on MyD88 and interleukin-18 and independent of Toll-like receptor 7 (TLR7)- and TLR9-mediated innate immune recognition. J Virol. 85(7):3385-96, 2011.

Numao A, Hosono K, Suzuki T, Hayashi I, Uematsu S, Akira S, Ogino Y, Kawauchi H, Unno N, Majima M. The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model. Biomed Pharmacother. 65(1):77-84, 2011.

Takemiya T, Matsumura K, Sugiura H, Yasuda S, Uematsu S, Akira S, Yamagata K. Endothelial microsomal prostaglandin E synthase-1 facilitates neurotoxicity by elevating astrocytic Ca2+ levels. Neurochem Int. 58(4):489-96, 2011.

Letran SE, Lee SJ, Atif SM, Uematsu S, Akira S, McSorley SJ. TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. Eur J Immunol. 41(1):29-38, 2011.