自然免疫受容体を介した腸管免疫の制御と全身免疫への影響の解析
Publicly Offered Research
Project Area | Preventive medicine through inflammation cellular sociology |
Project/Area Number |
18H05045
|
Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
|
Allocation Type | Single-year Grants |
Research Institution | Tokyo University of Science |
Principal Investigator |
岩倉 洋一郎 東京理科大学, 研究推進機構生命医科学研究所, 教授 (10089120)
|
Project Period (FY) |
2018-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2019: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2018: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
|
Keywords | C型レクチン / 大腸がん / 腸内細菌叢 / 腫瘍 / 免疫疾患 / シングルセル |
Outline of Annual Research Achievements |
C型レクチン受容体(CLR)は真菌などの細胞表面糖鎖を認識し、感染防御に重要な役割を果たすことを明らかにしてきた(Saijoら, Nat Immunol, 2007)。CLRのファミリーメンバーであるDectin-1はβグルカンの受容体であり、真菌感染防御と共に、腸管で抗菌ペプチドの分泌を制御しており、Dectin-1を阻害すると抗菌ペプチドが減少し、制御性T細胞(Treg)誘導性の細菌(Lactobacillus murinus)が増殖するために、Tregが増加して腸炎が抑制されることを示した(Tangら, Cell Host & Micro, 2015)。本研究では、この時の抗菌ペプチドの誘導機構を解析し、Dectin-1の下流でIL-17Fが誘導され、IL-17Fは単球を刺激することにより抗菌ペプチドを産生することを明らかにした(Kamiyaら, Mucosal Immunol, 2018)。また、IL-17Fによって誘導される抗菌ペプチドはL. murinusだけでなく、Clostridium XIVaなどのTreg誘導性の腸内細菌の増殖にも関与しており、IL-17Fを阻害すると、これらの菌が増殖し、Tregが増加して炎症が抑制されることを示した(Tangら, Nat Immunol, 2018)。これらの結果から、Dectin-1およびIL-17Fを阻害することにより、炎症性大腸炎を治療できることが解り、特許を申請した(岩倉、唐、PCT/JP2019/018787)。この他、種々のCLR欠損マウスを用いて、大腸ポリプの発症を検討し、大きな影響がでることを見出した。CLRは腫瘍細胞では発現しておらず、あるものは免疫担当細胞で発現して抗腫瘍免疫に影響を与えることが考えられたが、他のものは腸内細菌叢に影響を与え、間接的に腫瘍増殖に影響を与えていることが示唆された。
|
Research Progress Status |
令和元年度が最終年度であるため、記入しない。
|
Strategy for Future Research Activity |
令和元年度が最終年度であるため、記入しない。
|
Report
(2 results)
Research Products
(67 results)
-
-
-
-
-
[Journal Article] IL-1β Plays an Important Role in Pressure Overload-Induced Atrial Fibrillation in Mice2019
Author(s)
Matsushita N, Ishida N, Ibi M, Saito M, Takahashi M, Taniguchi S, Iwakura Y, Morino Y, Taira E, Sawa Y, Hirose M
-
Journal Title
Biological and Pharmaceutical Bulletin
Volume: 42
Issue: 4
Pages: 543-546
DOI
NAID
ISSN
0918-6158, 1347-5215
Year and Date
2019-04-01
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Spontaneous atopic dermataitis in mice with a defective skin barrier is independent of ILC2 and mediated by IL-1β.2019
Author(s)
Schwartz, C., Moran, T., Saunders, S. P., Kaszlikowska, A., Floudas, A., Bom, J., Nunez, G., Iwakura, Y., O’Neill, L., Irvine, A. D., McKenzie, A. N. J., Ogg, G., Walsh, P. T., Demengeot, J., and Fallon, P. G.
-
Journal Title
Allergy
Volume: 74
Issue: 10
Pages: 1920-1933
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment.2019
Author(s)
Drummond, R. A., Swamydas, M., Oikonomou, V., Zhai, B., Dambuza, I. M., Schaefer, B. C., Bohrer, A. C., Mayer-Barber, K. D., Lira, S. A., Iwakura, Y., Filler, S. G., Brown, G. D., Hube, B., Naglik, J. R., Hohl, T. M., and Lionakis, M. S.
-
Journal Title
Nat Immunol.
Volume: 20
Issue: 5
Pages: 559-570
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
[Journal Article] CCR8 leads to eosinophil migration and regulates neutrophil migration in murine allergic enteritis.2019
Author(s)
Blanco-Perez, F., Kato, Y., Gonzalez-Menendez, I., Laino, J., Ohbayashi, M., Burggraf, M., Krause, M., Kirberg, J., Iwakura, Y., Martella, M., Quintanilla-Martinez, L., Shibata, N., Vieths, S., Scheurer, S., and Toda, M.
-
Journal Title
Sci. Rep.
Volume: 9
Issue: 1
Pages: 9608-9608
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] AIM2 inflammasome-derived IL-1β induces postoperative ileus in mice.2019
Author(s)
Hupa, K. J., Stein, K., Schneider, R., Lysson, M., Schneiker, B., Hornung, V., Latz, E., Iwakura, Y., Kalff, J. C., and Wehner, S.
-
Journal Title
Sci. Rep.
Volume: 9
Issue: 1
Pages: 10602-10602
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis.2019
Author(s)
Sakurai K, Dainichi T, Garcet S, Tsuchiya S, Yamamoto Y, Kitoh A, Honda T, Nomura T, Egawa G, Otsuka A, Nakajima S, Matsumoto R, Nakano Y, Otsuka M, Iwakura Y, Grinberg-Bleyer Y, Ghosh S, Sugimoto Y, Guttman-Yassky E, Krueger JG, Kabashima K.
-
Journal Title
J Allergy Clin Immunol
Volume: 144(4)
Issue: 4
Pages: 1036-1049
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Defect of interferon γ leads to impaired wound healing through prolonged neutrophilic inflammatory response and enhanced MMP-2 activation.2019
Author(s)
Kanno E, Tanno H, Masaki A, Sasaki A, Sato N, Goto M, Shisai M, Yamaguchi K, Takagi N, Shoji M, Kitai Y, Sato K, Kasamatsu J, Ishii K, Miyasaka T, Kawakami K, Imai Y, Iwakura Y, Maruyama R, Tachi M, Kawakami K.
-
Journal Title
Int. J. Mol. Sci.
Volume: 20(22)
Issue: 22
Pages: 5657-5657
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Dectin-2-Mediated Signaling Leads to Delayed Skin Wound Healing through Enhanced Neutrophilic Inflammatory Response and Neutrophil Extracellular Trap Formation.2019
Author(s)
Miura T, Kawakami K, Kanno E, Tanno H, Tada H, Sato N, Masaki A, Yokoyama R, Kawamura K, Kitai Y, Takagi N, Yamaguchi K, Yamaguchi N, Kyo Y, Ishii K, Imai Y, Saijo S, Iwakura Y, Tachi M.
-
Journal Title
J Invest Dermatol
Volume: 139(3)
Issue: 3
Pages: 702-711
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
[Journal Article] IL-25 enhances Th17 cell-mediated contact dermatitis by promoting IL-1b production by dermal dendritic cells2018
Author(s)
Suto H, Nambu A, Morita H, Yamaguchi S, Numata T, Yoshizaki T, Shimura E, Arae K, Asada Y, Motomura K, Kaneko M, Abe T, Matsuda A, Iwakura Y, Okumura K, Saito H, Matsumoto K, Sudo K, Nakae S
-
Journal Title
J Allergy Clin Immunol
Volume: In press
Issue: 5
Pages: 1500-1509
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Inhibition of interleukin-1 suppresses angiotensin II-induced aortic inflammation and aneurysm formation.2018
Author(s)
Isoda K, Akita K, Kitamura K, Sato-Okabayashi Y, Kadoguchi T, Isobe S, Ohtomo F, Sano M, Shimada K, Iwakura Y, Daida H
-
Journal Title
Int J Cardiol
Volume: 270
Pages: 221-227
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] IL-6, IL-17 and Stat3 are required for auto-inflammatory syndrome development in mouse.2018
Author(s)
Oike T, Kanagawa H, Sato Y, Kobayashi T, Nakatsukasa H, Miyamoto K, Nakamura S, Kaneko Y, Kobayashi S, Harato K, Yoshimura A, Iwakura Y, Takeuchi T, Matsumoto M, Nakamura M, Niki Y, Miyamoto T.
-
Journal Title
Sci Rep.
Volume: -
Issue: 1
Pages: 15783-15783
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] MAIT cells protect against pulmonary Legionella longbeachae infection2018
Author(s)
Wang H, D'Souza C, Lim XY, Kostenko L, Pediongco TJ, Eckle SBG, Meehan BS, Shi M, Wang N, Li S, Liu L, Mak JYW, Fairlie DP, Iwakura Y, Gunnersen JM, Stent AW, Godfrey DI, Rossjohn J, Westall GP, Kjer-Nielsen L, Strugnell RA, McCluskey J, Corbett AJ, Hinks TSC, Chen Z.
-
Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 3350-3350
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] The ATP Transporter VNUT Mediates Induction of Dectin-1-Triggered Candida Nociception.2018
Author(s)
Maruyama K, Takayama Y, Sugisawa E, Yamanoi Y, Yokawa T, Kondo T, Ishibashi KI, Sahoo BR, Takemura N, Mori Y, Kanemaru H, Kumagai Y, Martino MM, Yoshioka Y, Nishijo H, Tanaka H, Sasaki A, Ohno N, Iwakura Y, Moriyama Y, Nomura M, Akira S, Tominaga M.
-
Journal Title
iScience
Volume: 6
Pages: 306-318
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] IL-36α from Skin-Resident Cells Plays an Important Role in the Pathogenesis of Imiquimod-Induced Psoriasiform Dermatitis by Forming a Local Autoamplification Loop.2018
Author(s)
Hashiguchi Y, Yabe R, Chung SH, Murayama MA, Yoshida K, Matsuo K, Kubo S, Saijo S, Nakamura Y, Matsue H, Iwakura Y.
-
Journal Title
J Immunol.
Volume: 201
Issue: 1
Pages: 167-182
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
[Journal Article] Suppression of IL-17F, but not of IL-17A, provides protection against colitis by inducing T(reg) cells through modification of the intestinal microbiota.2018
Author(s)
Tang C, Kakuta S, Shimizu K, Kadoki M, Kamiya T, Shimazu T, Kubo S, Saijo S, Ishigame H, Nakae S, Iwakura Y.
-
Journal Title
Nat Immunol.
Volume: 19
Issue: 7
Pages: 755-765
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] HER2 overexpression triggers an IL-1α pro-inflammatory circuit to drive tumorigenesis and promote chemotherapy resistance.2018
Author(s)
Liu, S., Lee, J. S., Jie, C., Park, M. H., Iwakura, Y., Patel, Y., Soni, M., Reisman, D., and Chen, H.
-
Journal Title
Cancer Res.
Volume: -
Issue: 8
Pages: 2040-2051
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] IL-1R2 deficiency suppresses dextran sodium sulfate-induced colitis in mice via regulation of microbiota.2018
Author(s)
Yoshida, K., Murayama, M., Shimizu, K., Tang, C., Katagiri, N., Matsuo, K., Fukai F., and Iwakura, Y.
-
Journal Title
Biochem. Biophys. Res. Commun.
Volume: 496
Issue: 3
Pages: 934-940
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Myeloid-derived interleukin-1β drives oncogenic KRAS-NF-κΒ addiction in malignant pleural effusion2018
Author(s)
Marazioti A, Lilis I, Vreka M, Apostolopoulou H, Kalogeropoulou A, Giopanou I, Giotopoulou GA, Krontira AC, Iliopoulou M, Kanellakis NI, Agalioti T, Giannou AD, Jones-Paris C, Iwakura Y, Kardamakis D, Blackwell TS, Taraviras S, Spella M, Stathopoulos GT.
-
Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 672-672
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
[Journal Article] Establishment and analysis of a novel mouse line carrying a conditional knockin allele of a cancer-specific FBXW7 mutation.2018
Author(s)
Ikenoue T, Terakado Y, Zhu C, Liu X, Ohsugi T, Matsubara D, Fujii T, Kakuta S,Kubo S, Shibata T, Yamaguchi K, Iwakura Y, Furukawa Y.
-
Journal Title
Sci Rep
Volume: 8
Issue: 1
Pages: 2021-2021
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Apaf1 plays a negative regulatory role in T cell responses by suppressing activation of antigen-stimulated T cells.2018
Author(s)
Tong, H., Miyake, Y., Mi-Ichi, F., Iwakura, Y., Hara, H. and Yoshida, H.
-
Journal Title
PLoS One
Volume: 13
Issue: 3
Pages: 0195119-0195119
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-