The analysis of antigen presenting cells in mouse and human intestinal lamina propria

2011 Fiscal Year Final Research Report

• Project/Area Number: 21689015
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: UEMATSU Satoshi 大阪大学, 免疫学フロンティア研究センター, 特任准教授 (50379088)
• Project Period (FY): 2009 – 2011
• Keywords: Toll-like receptor / マクロファージ / 樹状細胞 / 腸管粘膜固有層

Research Abstract

We found that CD103^+ DC in small intestine are divided into two subsets according to CD8αexpression. CD103^+ CD8α^+ DC express TLR3, 7 and 9 and induced Th1 response and Ag-specific IgG. In contrast, CD103^+ CD8α^+ DC express TLR5 and 9 and induced Th1 and Th17 responses, Ag-specific IgG and IgA and strong CTL activity. Accordingly, CD103^+ CD8α^+ LPDCs have the different function in active immunity from CD103^+ CD8α^-LPDCs.

Research Products

• [Journal Article] The protective role of TLR6 in a mouse model of asthma is mediated by IL-23 and IL-17A (2011)
  • Author(s): Moreira AP, Cavassani KA, Ismailoglu UB, Hullinger R, Dunleavy MP, Knight DA, Kunkel SL, Uematsu S, Akira S, Hogaboam CM
  • Journal Title: J Clin Inves Volume: 121(11) Pages: 4420-32
• [Journal Article] Microsomal prostaglandin E synthase-1 is involved in multiple steps of colon carcinogenesis (2011)
  • Author(s): Sasaki Y, Kamei D, Ishikawa Y, Ishii T, Uematsu S, Akira S, Murakami M, Hara S
  • Journal Title: Oncogene
• [Journal Article] A new subset of CD103^+ CD8a^+ DCs in the small intestine express TLR3, TLR7 and TLR9, and induce Th1 response and CTL activity (2011)
  • Author(s): Fujimoto K, Karuppuchamy T, Takemura N, Shimohigoshi M, Machida T, Haseda Y, Aoshi T, Ishii KJ, Akira S, Uematsu S
  • Journal Title: J Immunol Volume: 186(11) Pages: 6287-95
• [Journal Article] Silica Crystals and Aluminum Salts Regulate the Production of Prostaglandin in Macrophages via NALP3 Inflammasome-Independent Mechanisms (2011)
  • Author(s): Kuroda E, Ishii KJ, Uematsu S, Ohata K, Coban C, Akira S, Aritake K, Urade Y, Morimoto Y
  • Journal Title: Immunity Volume: 34(4) Pages: 514-26
• [Journal Article] Plasmacytoid Dendritic Cells Promote Host Defense against Acute Pneumovirus Infection via the TLR7-MyD88-Dependent Signaling Pathway (2011)
  • Author(s): 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
  • Journal Title: J Immunol Volume: 186(10) Pages: 5938-48
• [Journal Article] TLR5-Deficient Mice Lack Basal Inflammatory and Metabolic Defects but Exhibit Impaired CD4 T Cell Responses to a Flagellated Pathogen (2011)
  • Author(s): Letran SE, Lee SJ, Atif SM, Flores-Langarica A, Uematsu S, Akira S, Cunningham AF, McSorley SJ
  • Journal Title: J Immunol
• [Journal Article] Antiviral Protein Viperin Promotes Toll-like Receptor 7-and Toll-like Receptor 9-Mediated Type I Interferon Production in Plasmacytoid Dendritic Cells (2011)
  • Author(s): Saitoh T, Satoh T, Yamamoto N, Uematsu S, Takeuchi O, Kawai T, Akira S
  • Journal Title: Immunity Volume: 34(3) Pages: 352-63
• [Journal Article] Type I Interferon Signaling Regulates Ly6C Monocytes and Neutrophils during Acute Viral Pneumonia in Mice (2011)
  • Author(s): Seo SU, Kwon HJ, Ko HJ, Byun YH, Seong BL, Uematsu S, Akira S, Kweon MN
  • Journal Title: PLoS Pathog Volume: 7(2) Pages: e1001304
• [Journal Article] Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice (2011)
  • Author(s): Isono M, Suzuki T, Hosono K, Hayashi I, Sakagami H, Uematsu S, Akira S, Declerck YA, Okamoto H, Majima M
  • Journal Title: Life Sci Volume: 88(15-16) Pages: 693-700
• [Journal Article] 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 (2011)
  • Author(s): Lousberg EL, Diener KR, Fraser CK, Phipps S, Foster PS, Chen W, Uematsu S, Akira S, Robertson SA, Brown MP, Hayball JD
  • Journal Title: J Virol Volume: 85(7) Pages: 3385-96
• [Journal Article] The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model (2011)
  • Author(s): Numao A, Hosono K, Suzuki T, Hayashi I, Uematsu S, Akira S, Ogino Y, Kawauchi H, Unno N, Majima M
  • Journal Title: Biomed Pharmacother Volume: 65(1) Pages: 77-84
• [Journal Article] Endothelial microsomal prostaglandin E synthase-1 facilitates neurotoxicity by elevating astrocytic Ca2+ levels (2011)
  • Author(s): Takemiya T, Matsumura K, Sugiura H, Yasuda S, Uematsu S, Akira S, Yamagata K
  • Journal Title: Neurochem Int Volume: 58(4) Pages: 489-96
• [Journal Article] TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity (2011)
  • Author(s): Letran SE, Lee SJ, Atif SM, Uematsu S, Akira S, McSorley SJ
  • Journal Title: Eur J Immunol Volume: 41(1) Pages: 29-38
• [Journal Article] The innate immune system in the intestine (2010)
  • Author(s): Uematsu S, Fujimoto K
  • Journal Title: Microbiol Immunol Volume: 54(11) Pages: 645-57
• [Journal Article] Role of adrenomedullin in Lyme disease (2010)
  • Author(s): Marre ML, Darcy CT, Yinh J, Akira S, Uematsu S, Steere AC, Hu LT
  • Journal Title: Infect Immun Volume: 78(12) Pages: 5307-13
• [Journal Article] Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers (2010)
  • Author(s): Ae T, Ohno T, Hattori Y, Suzuki T, Hosono K, Minamino T, Sato T, Uematsu S, Akira S, Koizumi W, Majima M
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 299(5) Pages: G1139-46
• [Journal Article] Toll-like receptor 4(TLR4), but not TLR3 or TLR9, knock-out mice have neuroprotective effects against focal cerebral ischemia (2010)
  • Author(s): Hyakkoku K, Hamanaka J, Tsuruma K, Shimazawa M, Tanaka H, Uematsu S, Akira S, Inagaki N, Nagai H, Hara H
  • Journal Title: Neuroscience Volume: 171(1) Pages: 258-67
• [Journal Article] Pathways regulating cytosolic phospholipase A2 activation and eicosanoid production in macrophages by Candida albicans (2010)
  • Author(s): Suram S, Gangelhoff TA, Taylor PR, Rosas M, Brown GD, Bonventre JV, Akira S, Uematsu S, Williams DL, Murphy RC, Leslie CC
  • Journal Title: J Biol Chem Volume: 285(40) Pages: 30676-85
• [Journal Article] Microsomal prostaglandin E synthase-1 contributes to ischaemic excitotoxicity through prostaglandin E2 EP3 receptors (2010)
  • Author(s): Ikeda-Matsuo Y, Tanji H, Ota A, Hirayama Y, Uematsu S, Akira S, Sasaki Y
  • Journal Title: Br J Pharmacol Volume: 160(4) Pages: 847-59
• [Journal Article] mPGES-1-expressing bone marrow-derived cells enhance tumor growth and angiogenesis in mice (2010)
  • Author(s): Kamata H, Hosono K, Suzuki T, Ogawa Y, Kubo H, Katoh H, Ito Y, Uematsu S, Akira S, Watanabe M, Majima M
  • Journal Title: Biomed Pharmacother Volume: 64(6) Pages: 409-16
• [Journal Article] Pathogenic Vibrio activate NLRP3 inflammasome via cytotoxins and TLR/ nucleotide-binding oligomerization domain-mediated NF-kappa B signaling (2010)
  • Author(s): Toma C, Higa N, Koizumi Y, Nakasone N, Ogura Y, McCoy AJ, Franchi L, Uematsu S, Sagara J, Taniguchi S, Tsutsui H, Akira S, Tschopp J, Nunez G, Suzuki T
  • Journal Title: J Immunol Volume: 184(9) Pages: 5287-97
• [Journal Article] Microsomal prostaglandin E synthase-1 and cyclooxygenase-2 are both required for ischaemic excitotoxicity (2010)
  • Author(s): Ikeda-Matsuo Y, Hirayama Y, Ota A, Uematsu S, Akira S, Sasaki Y
  • Journal Title: Br J Pharmacol Volume: 159(5) Pages: 1174-86
• [Journal Article] Airway Epithelial Indoleamine 2, 3-Dioxygenase Inhibits CD4+ T Cells During Aspergillus fumigatus Antigen Exposure (2010)
  • Author(s): Paveglio SA, Allard J, Foster Hodgkins SR, Ather J, Bevelander M, Mayette Campbell J, Whittaker Leclair LA, McCarthy SM, van der Vliet A, Suratt BT, Boyson JE, Uematsu S, Akira S, Poynter ME
  • Journal Title: Am J Respir Cell Mol Biol
• [Journal Article] Toll-like receptor 6 drives interleukin-17A expression during experimental hypersensitivity pneumonitis (2010)
  • Author(s): Fong DJ, Hogaboam CM, Matsuno Y, Akira S, Uematsu S, Joshi AD
  • Journal Title: Immunology Volume: 130(1) Pages: 125-36
• [Journal Article] Plasmacytoid dendritic cell-derived type I interferon is crucial for the adjuvant activity of Toll-like receptor 7 agonists (2010)
  • Author(s): Rajagopal D, Paturel C, Morel Y, Uematsu S, Akira S, Diebold SS
  • Journal Title: Blood Volume: 115(10) Pages: 1949-57
• [Journal Article] TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88 independent, whereas MyD88 is required to clear infection (2010)
  • Author(s): Burns E, Eliyahu T, Uematsu S, Akira S, Nussbaum G
  • Journal Title: J Immunol Volume: 184(3) Pages: 1455-62
• [Journal Article] Prostaglandin E(2) exerts homeostatic regulation of pulmonary vascular remodeling in allergic airway inflammation (2010)
  • Author(s): Lundequist A, Nallamshetty SN, Xing W, Feng C, Laidlaw TM, Uematsu S, Akira S, Boyce JA
  • Journal Title: J Immunol Volume: 184(1) Pages: 433-41
• [Journal Article] Critical role of TLR7 in the acceleration of systemic lupus erythematosus in TLR9-deficient mice (2010)
  • Author(s): Santiago-Raber ML, Dunand-Sauthier I, Wu T, Li QZ, Uematsu S, Akira S, Reith W, Mohan C, Kotzin BL, Izui S
  • Journal Title: J Autoimmun Volume: 34(4) Pages: 339-48
• [Journal Article] Intestine and Innate Immunity (2009)
  • Author(s): Uematsu S, Akira S
  • Journal Title: Bioscience and Microflora Volume: 28(3) Pages: 69-74
• [Journal Article] Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis (2009)
  • Author(s): Kihara Y, Matsushita T, Kita Y, Uematsu S, Akira S, Kira J, Ishii S, Shimizu T
  • Journal Title: Proc Natl Acad Sci USA Volume: 106(51) Pages: 21807-12
• [Journal Article] Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis (2009)
  • Author(s): Kamei D, Murakami M, Sasaki Y, Nakatani Y, Majima M, Ishikawa Y, Ishii T, Uematsu S, Akira S, Hara S, Kudo I
  • Journal Title: Biochem J Volume: 425(2) Pages: 361-71
• [Journal Article] TLR7 modulates anti-nucleosomal autoantibody isotype and renal complement deposition in mice exposed to syngeneic late apoptotic cells (2009)
  • Author(s): Pan ZJ, Maier S, Schwarz K, Azbill J, Akira S, Uematsu S, Farris AD
  • Journal Title: Ann Rheum Dis Volume: 69(6) Pages: 1195-9
• [Journal Article] Endothelial microsomal prostaglandin E synthase-1 exacerbates neuronal loss induced by kainate (2009)
  • Author(s): Takemiya T, Matsumura K, Sugiura H, Maehara M, Yasuda S, Uematsu S, Akira S, Yamagata K
  • Journal Title: J Neurosci Res Volume: 88(2) Pages: 381-90
• [Journal Article] NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection (2009)
  • Author(s): Kayama H, Koga R, Atarashi K, Okuyama M, Kimura T, Mak TW, Uematsu S, Akira S, Takayanagi H, Honda K, Yamamoto M, Takeda K
  • Journal Title: PLoS Pathog Volume: 5(7) Pages: e1000514
• [Journal Article] Downstream signals for MyD88-mediated phagocytosis of Borrelia burgdorferi can be initiated by TRIF and are dependent on PI3K (2009)
  • Author(s): Shin OS, Miller LS, Modlin RL, Akira S, Uematsu S, Hu LT
  • Journal Title: J Immunol Volume: 183(1) Pages: 491-8
• [Journal Article] PolyI : C-induced reduction in uptake of soluble antigen is independent of dendritic cell activation (2009)
  • Author(s): Tirapu I, Giquel B, Alexopoulou L, Uematsu S, Flavell R, Akira S, Diebold SS
  • Journal Title: Int Immunol Volume: 21(7) Pages: 871-9
• [Journal Article] Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin (2009)
  • Author(s): Bates JT, Uematsu S, Akira S, Mizel SB
  • Journal Title: J Immunol Volume: 182(12) Pages: 7539-47
• [Journal Article] Baculovirus induces type I interferon production through toll-like receptor-dependent and-independent pathways in a cell-type-specific manner (2009)
  • Author(s): Abe T, Kaname Y, Wen X, Tani H, Moriishi K, Uematsu S, Takeuchi O, Ishii KJ, Kawai T, Akira S, Matsuura Y
  • Journal Title: J Virol Volume: 83(15) Pages: 7629-40
• [Journal Article] Radioresistant cells expressing TLR5 control the respiratory epithelium' s innate immune responses to flagellin (2009)
  • Author(s): Janot L, Sirard JC, Secher T, Noulin N, Fick L, Akira S, Uematsu S, Didierlaurent A, Hussell T, Ryffel B, Erard F
  • Journal Title: Eur J Immunol Volume: 39(6) Pages: 1587-96
• [Journal Article] Toll-like receptor 3 enhances late-phase reaction of experimental allergic conjunctivitis (2009)
  • Author(s): Ueta M, Uematsu S, Akira S, Kinoshita S
  • Journal Title: J Allergy Clin Immunol Volume: 123(5) Pages: 1187-9
• [Journal Article] Th2 allergic immune response to inhaled fungal antigens is modulated by TLR-4-independent bacterial products (2009)
  • Author(s): Allard JB, Rinaldi L, Wargo MJ, Allen G, Akira S, Uematsu S, Poynter ME, Hogan DA, Rincon M, Whittaker LA
  • Journal Title: Eur J Immunol Volume: 39(3) Pages: 776-88
• [Journal Article] Bacterial endotoxin induces the release of high mobility group box 1 via the IFN-beta signaling pathway (2009)
  • Author(s): Kim JH, Kim SJ, Lee IS, Lee MS, Uematsu S, Akira S, Oh KI
  • Journal Title: J Immunol Volume: 182(4) Pages: 2458-66
• [Journal Article] Toll-like receptor 2 deficiency is associated with enhanced severity of group B streptococcal disease (2009)
  • Author(s): Puliti M, Uematsu S, Akira S, Bistoni F, Tissi L
  • Journal Title: Infect Immun Volume: 77(4) Pages: 1524-31
• [Journal Article] Induction of adaptive immunity by flagellin does not require robust activation of innate immunity (2009)
  • Author(s): Sanders CJ, Franchi L, Yarovinsky F, Uematsu S, Akira S, Nunez G, Gewirtz AT
  • Journal Title: Eur J Immunol Volume: 39(2) Pages: 359-71
• [Journal Article] Pivotal Advance : Toll-like receptor regulation of scavenger receptor-A-mediated phagocytosis (2009)
  • Author(s): Amiel E, Alonso A, Uematsu S, Akira S, Poynter ME, Berwin B
  • Journal Title: J Leukoc Biol Volume: 85(4) Pages: 595-605
• [Presentation] 消化管自然免疫からみた食物アレルギーの成立および耐性獲得 (2011)
  • Author(s): 植松智
  • Organizer: 第5回子どもの食育を考えるフォーラム
  • Place of Presentation: 大阪医科大学
  • Year and Date: 2011-01-29
• [Presentation] Antigen-specific cytokine profiles and phenotypes in small intestinal Th17 cells (2010)
  • Author(s): 植松智
  • Organizer: シンポジウム第10回淡路島感染症免疫フォーラム
  • Place of Presentation: 淡路
  • Year and Date: 20100907-10
• [Presentation] Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 (2009)
  • Author(s): Uematsu S
  • Organizer: Symposium The 2009 Fall Conference of The Korean Association of Immunologists
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20091109-10
• [Presentation] 特別講演臨床医が知っておきたい自然免疫の知識-基本から最近の知見まで- (2009)
  • Author(s): 植松智
  • Organizer: 第149回大阪小児科医会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-09-12
• [Presentation] 特別講演自然免疫と消化管 (2009)
  • Author(s): 植松智
  • Organizer: 第23回大阪小児栄養消化器病懇話会
  • Place of Presentation: 大阪
  • Year and Date: 2009-06-06
• [Book] 臨床粘膜免疫学分泌型IgA誘導における分子・細胞環境粘膜系樹状細胞(実行組織) (2010)
  • Author(s): 植松智
  • Total Pages: 275-280
  • Publisher: シナジー
• [Book] 審良静男.臨床粘膜免疫学粘膜における自然免疫TLRs・RLRs (2010)
  • Author(s): 植松智
  • Total Pages: 66-78
  • Publisher: シナジー
• [Book] 蛋白質核酸酵素増刊腸内細菌感染におけるTLR5陽性樹状細胞の免疫応答 (2009)
  • Author(s): 植松智
  • Total Pages: 1020-1026
  • Publisher: 共立出版
• [Book] 感染・炎症・免疫腸管粘膜固有層のTLR5陽性樹状細胞の免疫制御 (2009)
  • Author(s): 植松智
  • Total Pages: 26-33
  • Publisher: 医薬の門社
• [Book] 臨床免疫・アレルギー科小腸粘膜固有層TLR5+樹状細胞によるIgA産生とTh17細胞の誘導 (2009)
  • Author(s): 藤本康介, 植松智, 審良静男
  • Total Pages: 207-216
  • Publisher: 科学評論社
• [Remarks]
  • URL: http://hostdefense.ifrec.osaka-u.ac.jp/ja/index.html