Molecular mechanisms on antigen presenting cell function and generation
Project/Area Number |
20H03505
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49070:Immunology-related
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Research Institution | Wakayama Medical University |
Principal Investigator |
Kaisho Tsuneyasu 和歌山県立医科大学, 先端医学研究所, 教授 (60224325)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2020: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
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Keywords | 樹状細胞 / 炎症 / 遺伝子改変マウス / I型インターフェロン / DNAセンサー / プロテアソーム / 自己炎症 / 免疫不全 / 前駆細胞 / 自己炎症性疾患 / シグナル伝達 / 発がん |
Outline of Research at the Start |
樹状細胞を中心とした抗原提示細胞はいろいろなサブセットに分かれていて、サブセット特有の機能的特性により免疫応答に関与する。これまで、遺伝子改変マウスを用いた解析により、ケモカイン受容体XCR1を発現する樹状細胞サブセット(XCR1+DC)の動態や機能的意義を明らかにしてきた。本研究では、XCR1+DCの生成が障害されたマウス、XCR1+DCを構成的に欠失するマウスを用いて、抗原提示細胞の機能的分化を制御する分子機構、および抗原提示細胞の新たな機能的意義の解明を目指す。
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Outline of Final Research Achievements |
By establishing and analyzing mouse models of autoinflammatory diseases, we attempted to elucidate the molecular mechanisms for regulating antigen-presenting cell function and differentiation. By analyzing the gene variants of COPA, a functional molecule involved in the protein transport, we clarified the novel pathological mechanisms leading to overproduction of type I interferon (IFN) from DNA sensor-stimulated dendritic cells (DCs). By analyzing the gene variants of beta1i subunit of the proteasome, a protein complex that degrades unnecessary or misfolded proteins, proteasome dysfunction can cause defects in DC generation.
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Academic Significance and Societal Importance of the Research Achievements |
自己炎症性疾患患者の遺伝子バリアントをマウスに導入することにより、ヒトの病態をマウスで再現すると共に、抗原提示細胞の機能や分化に異常を来す病態が明らかになった。本研究により、自己炎症性疾患ばかりでなく、様々な炎症病態の解明が進み、新たな炎症制御剤が見出されることが期待される。
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Report
(4 results)
Research Products
(92 results)
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[Journal Article] XCR1+ DCs are critical for T cell-mediated immunotherapy of chronic viral infections.2023
Author(s)
E. Domenjo Vila, V. Casella, R. Iwabuchi, E. Fossum, M. Pedragosa, Q. Castellvi, P. Cebollada Rica, T. Kaisho, K. Terahara, G. Bocharov, J. Argilaguet, A. Meyerhans.
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Journal Title
Cell Rep
Volume: 42
Issue: 2
Pages: 112123-112123
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Type 1 conventional dendritic cells maintain and guide the differentiation of precursors of exhausted T cells in distinct cellular niches2022
Author(s)
S. Daehling, A. M. Mansilla, K. Knopper, A. Grafen, D. T Utzschneider, M. Ugur, P. G Whitney, A. Bachem, P. Arampatzi, F. Imdahl, T. Kaisho, D. Zehn, F. Klauschen, N. Garbi, A. Kallies, A.-E. Saliba, G. Gasteiger, S. Bedoui, W. Kastenmuller.
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Journal Title
Immunity
Volume: 55
Issue: 4
Pages: 656-670
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Distinct myeloid antigen-presenting cells dictate differential fates of tumor-specific CD8+ T cells in pancreatic cancer.2022
Author(s)
A. L. Burrack, Z. C. Schmiechen, M. T. Patterson, E. A. Miller, E. J. Spartz, M. R. Rollins, J. F. Raynor, J. S. Mitchell, T. Kaisho, B. T. Fife, I. M. Stromnes.
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Journal Title
JCI Insight
Volume: 7
Issue: 7
Pages: 151593-151593
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The liver contains distinct interconnected networks of CX3CR1+ macrophages, XCR1+ type 1 and CD301a+ type 2 conventional dendritic cells embedded within portal tracts2022
Author(s)
K. English, S. Yang Tan, R. Kwan, L. E Holz, F. Sierro, C. McGuffog, T. Kaisho, W. R Heath, K. Pa MacDonald, G. W McCaughan, D. G Bowen, P. Bertolino.
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Journal Title
Immunol Cell Biol
Volume: 100
Issue: 6
Pages: 394-408
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A vaccine targeting resistant tumours by dual T cell plus NK cell attack2022
Author(s)
S. Badrinath, MO. Dellacherie, A. Li, S. Zheng, X. Zhang, M. Sobral, JW. Pyrdol, KL. Smith, Y. Lu, S. Haag, H. Ijaz, F. Connor-Stroud, T. Kaisho, G. Dranoff, GC. Yuan, DJ. Mooney, KW. Wucherpfennig.
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Journal Title
Nature
Volume: 606
Issue: 7916
Pages: 992-998
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Depletion of cDC1 cells upon immunotherapy of established tumors precludes efficacy. Cancer Research Depletion of Conventional Type-1 Dendritic Cells in Established Tumors Suppresses Immunotherapy Efficacy2022
Author(s)
A. Teijeira, S. Garasa, C. luri, C. de Andrea, M. Gato, C. Molina, T. Kaisho, A. Cirella, A. Azpilikueta, S. Wculek, J. Egea, I. Olivera, I. Rodriguez, A. Rouzaut, V. Verkhusha, K. Valencia, D. Sancho, P. Berraondo, I. Melero.
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Journal Title
Cancer Research
Volume: 82
Issue: 23
Pages: 4373-4385
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[Journal Article] Augmentation of STING‐induced type I interferon production in COPA syndrome2021
Author(s)
Kato Takashi、Yamamoto Masaki、Honda Yoshitaka、Orimo Takashi、Sasaki Izumi、Murakami Kohei、Hemmi Hiroaki、Fukuda‐Ohta Yuri、Isono Kyoichi、Takayama Saki、Nakamura Hidenori、Otsuki Yoshiro、Miyamoto Toshiaki、Takita Junko、Yasumi Takahiro、Nishikomori Ryuta、Matsubayashi Tadashi、Izawa Kazushi、Kaisho Tsuneyasu
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Journal Title
Arthritis & Rheumatology
Volume: in press
Issue: 11
Pages: 2105-2115
DOI
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Peer Reviewed / Open Access
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[Journal Article] Radiation inducible MafB gene is required for thymic regeneration2021
Author(s)
Daiki Hashimoto, Jose Gabriel R. Colet, Aki Murashima, Kota Fujimoto, Yuko Ueda, Kentaro Suzuki, Taiju Hyuga, Hiroaki Hemmi, Tsuneyasu Kaisho, Satoru Takahashi, Yousuke Takahama and Gen Yamada1
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Journal Title
Scientific Reports
Volume: -
Issue: 1
Pages: 10439-10439
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] IFNβ Is a Potent Adjuvant for Cancer Vaccination Strategies.2021
Author(s)
K. M. Audsley, T. Wagner, C. Ta, H. V. Newnes, A. C. Buzzai, S. A. Barnes, B. Wylie, J. Armitage, T. Kaisho, A. Bosco, A. McDonnell, M. Cruickshank, V. S. Fear, B. Foley, J. Waithman
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Journal Title
Frontiers Immunol
Volume: 12
Pages: 735133-735133
DOI
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Heterozygous missense variant of the proteasome subunit β-type 9 causes neonatal-onset autoinflammation and immunodeficiency2021
Author(s)
Kanazawa N, Hemmi H, Kinjo N, Ohnishi H, Hamazaki J, M.H, K.A, M.T, H.S, K.N, K.S, H.Y, I.K, N.R, T.M, Y.Y, T.S, O.T, O.T, K.T, S.I, F.Y, W.N, I.Y, K.K, O.S, T.T, N.K, M.S, Y.K, Kaisho T
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 0-0
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Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Hypomorphic mutation of Lig4 gene in mice predisposes to intestinal inflammation driven by Th1 cells2022
Author(s)
Y. Yamashita, T. Kato, H. Kosako, S. Iwabuchi, K. Tanaka, K. Nakashima, I. Sasaki, S. Hashimoto, K. Ohshima, T. Kaisho, T. Sonoki, S. Tamura.
Organizer
第84回日本血液学会学術集会
Related Report
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[Presentation] Activation of type 1 interferon signaling in dendritic cells and T cells of the mouse model of COPA syndrome.2022
Author(s)
T.Kato, R.Yamasaki, N.W-Nishiyama. I.Sasaki, S.Kaji, K.Murakami, H.Hemmi, Y.Honda, K.Izawa, Y.Otsuki, T.Matsubayashi, R.Nishikomori, T.Kaisho.
Organizer
第29回日本免疫毒性学会学術年会
Related Report
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[Presentation] Immunotherapy of chronic virus infections: exhausted CD8+ T cell subsets are differentially regulated by XCR1+ DC.2022
Author(s)
A.Meyerhans, E.D-Vila, V.Casella, R.Iwabuxhi, E.Fossum, M.Pedragosa, Q.Castellvi, T.Kaisho, K.Terahara, G.Bocharov, J.Argilaguet.
Organizer
The 16th International Symposium on Dendritic Cells 2022
Related Report
Int'l Joint Research
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[Presentation] An endoplasmic reticulum stress sensor IRE1α is involved in cholera toxin-induced interleukin-1β production from tissue resident macrophages2021
Author(s)
I. Sasaki, Y. Fukuda-Ohta, N. Wakaki-Nishiyama, C. Nakai, S. Morita, D. Okuzaki, M. Kaku, K. Sawase, T. Kato, T. Orimo, K. Furukawa, T. Kaisho
Organizer
第28回日本免疫毒性学会学術集会
Related Report
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[Presentation] Unique location in the immunoproteasome complex of a variant causing proteasome-associated autoinflammatory syndrome with immunodeficiency2021
Author(s)
N. Kanazawa, H. Hemmi, N. Kinjo, H. Ohnishi, J. Hamazaki, H. Mishima, A. Kinoshita, T. Mizushima, S. Murata, K. Yoshiura, T. Kaisho
Organizer
第50回日本免疫学会総会
Related Report
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[Presentation] Sublingual dendritic cell (DC) - T cell clusters and distribution of DCs in the oral cavity2021
Author(s)
Y. Kusumoto, T. Kaisho, H. Hemmi, T. Katakai, T. Honda, J. Kikuta, K. Kataoka, T. Moriya, M. Ishii, K. Kabashima, M. Tomura
Organizer
第50回日本免疫学会総会
Related Report
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[Presentation] Interstitial Lung Disease and abnormal STING activation in COPA V242G heterozygous variant mice2021
Author(s)
T. Kato, T. Orimo, Y. Fukuda-Ohta, N. Wakaki-Nishiyama, C. Nakai, I. Sasaki, K. Murakami, H. Hemmi, Y. Honda, K. Izawa, Y. Otsuki, T. Matsubayashi, R. Nishikomori, T. Kaisho
Organizer
IEIIS2021: 16th Meeting of the International Endotoxin and Innate Immunity Society (26tth Japanese Endotoxin and innate Immunity Society
Related Report
Int'l Joint Research
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[Presentation] Critical roles of IRE1α in cholera toxin-induced interleukin-1β production from resident peritoneal macrophages2021
Author(s)
I. Sasaki, Y. Fukuda-Ohta, N. Wakaki-Nishiyama, C. Nakai, S. Morita, D. Okuzaki, M. Kaku, K. Sawase, A. Yamamoto, T. Kato, T. Orimo, K. Furukawa, T. Kaisho
Organizer
IEIIS2021: 16th Meeting of the International Endotoxin and Innate Immunity Society (26tth Japanese Endotoxin and innate Immunity Society)
Related Report
Int'l Joint Research
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[Presentation] Role of cross-presenting dendritic cells in anti-PD-L1 immunotherapy of chronic viral infections.2020
Author(s)
E. Domenjo-Vila, V. Casella, R. Iwabuchi, E. Fossum, M. Pedragosa, Q. Castellvi, T. Kaisho, K. Terahara, G. Bocharov, J. Argilaguet, A. Meyerhans.
Organizer
2nd Research Symposium on Coronavirus / XIX Jornada de Virologia / Virology Meeting 2020. Online meeting.
Related Report
Int'l Joint Research
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