Elucidation of molecular mechanism of TNF receptor-associated periodic syndrome by cell technology and multi-omics analysis
Project/Area Number |
19K08299
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
|
Research Institution | Kurume University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
井澤 和司 京都大学, 医学研究科, 助教 (90634931)
|
Project Period (FY) |
2019-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | TNF受容体関連症候群 / 自己炎症性疾患 / 自己炎症性症候群 / iPS細胞 / TRAPS / iPS-ML / TNF受容体関連周期性症候群 / 疾患特異的iPS細胞 / iPS細胞由来細胞株 / マクロファージ / 自己炎症症候群 / マルチオミックス解析 / オミックス解析 |
Outline of Research at the Start |
TNF受容体関連周期性症候群(TRAPS)は5日以上持続する弛張熱、漿膜炎を特徴とする自己炎症性疾患で、炎症の分子機序ならびに診断に有用なバイオマーカーが未同定である。本研究では、TRAPSの患者検体、疾患特異的iPS細胞に対してオミックス解析を行うことにより、TRAPS炎症病態の解析ならびに再現系構築を行う。また、疾患特異的iPS細胞より漿膜マクロファージを作成、臓器特異的炎症における臓器特異的マクロファージの関与について検討する。以上の研究により、TRAPSの炎症病態の分子機序解明、TRAPSの診断法を確立、TRAPSの診断ならびに治療の基盤構築を目指す。
|
Outline of Final Research Achievements |
TNF receptor-associated periodic syndrome (TRAPS) is an autoinflammatory disease characterized by flaccid fever and serositis lasting more than 5 days, and the molecular mechanism of inflammation and useful biomarkers for diagnosis have not been identified. In this study, we performed omics analysis of TRAPS patient samples and disease-specific iPS cells to analyze the pathogenesis of TRAPS inflammation . First, we generated disease-specific iPS cells from 2 TRAPS patients (T50M) and established the protocol to make macrophage cells from iPS cells. Furthermore, by forced expression of cMYC, BMI1, and MDM2 in iPS cells, a macrophage cell line, iPS-ML, was generated, and a macrophage differentiation system was constructed from these cells for pathological analysis. We also analyzed 2 TRAPS-like patients with unknown fever and diagnosed a JMML-like patient with NRAS somatic mosaicism mutation and a patient with cerebellar tumors with IL-6-producing tumors.
|
Academic Significance and Societal Importance of the Research Achievements |
TRAPSは病態の分子機序が不明であり、TNFRSF1A遺伝子変異がどのように炎症機序を来すか、治療、診断における未解決の問題として存在する。本研究によりTRAPSの主病態を形成すると考えられている疾患関連変異を有するヒトマクロファージ産生系が構築された。同細胞と患者細胞の解析を併せたオミックス解析を行うことによりTRAPSの分子病態の解析が可能となった。この手法を遺伝性炎症性疾患である自己炎症性疾患に応用することにより同疾患の病態解析を加速し、また、臓器特異的マクロファージ分化を試みることにより未だ未解決である臓器特異的な病態の解明につながる可能性を示した。
|
Report
(4 results)
Research Products
(27 results)
-
[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
-
Journal Title
Arthritis & Rheumatology
Volume: in press
Issue: 11
Pages: 2105-2115
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Rapid Flow Cytometry-Based Assay for the Functional Classification of MEFV Variants2021
Author(s)
Honda Y, Maeda Y, Izawa K, Shiba T, Tanaka T, Nakaseko H, Nishimura K, Mukoyama H, Isa-Nishitani M, Miyamoto T, Nihira H, Shibata H, Hiejima E, Ohara O, Takita J, Yasumi T, Nishikomori R.
-
Journal Title
J Clin Immunol.
Volume: Online ahead of print.
Issue: 6
Pages: 1187-1197
DOI
Related Report
Peer Reviewed / Open Access
-
-
[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
-
Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 0-0
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Hematopoietic Cell Transplantation Ameliorates Autoinflammation in A20 Haploinsufficiency2021
Author(s)
Shiraki, M. Williams, E. Yokoyama, N. Shinoda, K. Nademi, Z. Matsumoto, K. Nihira, H. Honda, Y. Izawa, K. Nishikomori, R. Slatter, M. A. Cant, A. J. Gennery, A. R. Ohnishi, H. Kanegane, H.
-
Journal Title
J Clin Immunol
Volume: 41
Issue: 8
Pages: 1954-1956
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
[Journal Article] ISSAID/EMQN Best Practice Guidelines for the Genetic Diagnosis of Monogenic Autoinflammatory Diseases in the Next-Generation Sequencing Era2020
Author(s)
Shinar, Y. Ceccherini, I. Rowczenio, D. Aksentijevich, I. Arostegui, J. Ben-Chetrit, E. Boursier, G. Gattorno, M. Hayrapetyan, H. Ida, H. Kanazawa, N. Lachmann, H. J. Mensa-Vilaro, A. Nishikomori, R. van Gijn, M. E. Touitou, I..
-
Journal Title
Clinical Chemistry
Volume: 66
Issue: 4
Pages: 525-536
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] Immunophenotyping of A20 haploinsufficiency by multicolor flow cytometry2020
Author(s)
Kadowaki, T. Ohnishi, H. Kawamoto, N. Kadowaki, S. Hori, T. Nishimura, K. Kobayashi, C. Shigemura, T. Ogata, S. Inoue, Y. Hiejima, E. Izawa, K. Matsubayashi, T. Matsumoto, K. Imai, K. Nishikomori, R. Ito, S. Kanegane, H. Fukao, T.
-
Journal Title
Clinical Immunology
Volume: 216
Pages: 108441-108441
DOI
Related Report
Peer Reviewed
-
[Journal Article] Functional analysis of a novel G87V TNFRSF1A mutation in patients with TNF receptor-associated periodic syndrome2019
Author(s)
Tsuji, S. Matsuzaki, H. Iseki, M. Nagasu, A. Hirano, H. Ishihara, K. Ueda, N. Honda, Y. Horiuchi, T. Nishikomori, R. Morita, Y. Mukai, T.
-
Journal Title
Clin Exp Immunol
Volume: 198
Issue: 3
Pages: 416-429
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
[Journal Article] Functional evaluation of the pathological significance of MEFV variants using induced pluripotent stem cell-derived macrophages2019
Author(s)
Shiba, T. Tanaka, T. Ida, H. Watanabe, M. Nakaseko, H. Osawa, M. Shibata, H. Izawa, K. Yasumi, T. Kawasaki, Y. Saito, M. K. Takita, J. Heike, T. Nishikomori, R.
-
Journal Title
J Allergy Clin Immunol
Volume: 144
Issue: 5
Pages: 1438-1441
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
[Presentation] A case report of Hermansky-Pudlak type 2 in comparison with Hermansky-Pudlak type 1 in onePID center.2020
Author(s)
西小森隆太, 渡邊順子, 田中征治, 島さほ, 北城恵史郎, 水落建輝, 石原潤, 柴田洋史, 八角高裕, 井澤和司, 岡村賢, 林昌弘, 鈴木民夫, 田代克弥, 冨野広通, 江頭智子, 高柳俊光, 山下裕史朗.
Organizer
第3回日本免疫不全・自己炎症学会総会・学術集会
Related Report
-
[Presentation] 免疫疾患の遺伝的背景 新規機能解析系によるMEFVバリアントの病原性評価・分類の試み.2020
Author(s)
前田由可子, 本田吉孝, 井澤和司, 芝 剛, 田中孝之, 東口素子, 加藤健太郎, 宮本尚幸, 伊佐真彦[西谷], 仁平寛士, 柴田洋史, 日衛嶋栄太郎, 滝田順子, 西小森隆太.
Organizer
第43回日本臨床免疫学会総会
Related Report
-
-