mRNA代謝が司る免疫制御機構の解明

• Project/Area Number: 18H05278
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section H
• Research Institution: Kyoto University
• Principal Investigator: 竹内 理 京都大学, 医学研究科, 教授 (10379092)
• Co-Investigator(Kenkyū-buntansha): 植畑 拓也 京都大学, 医学研究科, 助教 (50785970) ; 三野 享史 京都大学, 医学研究科, 助教 (60646149)
• Project Period (FY): 2018-06-11 – 2023-03-31
• Project Status: Granted (Fiscal Year 2021)
• Budget Amount: ¥193,570,000 (Direct Cost: ¥148,900,000、Indirect Cost: ¥44,670,000); Fiscal Year 2022: ¥33,280,000 (Direct Cost: ¥25,600,000、Indirect Cost: ¥7,680,000); Fiscal Year 2021: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2020: ¥37,960,000 (Direct Cost: ¥29,200,000、Indirect Cost: ¥8,760,000); Fiscal Year 2019: ¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000); Fiscal Year 2018: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
• Keywords: 免疫応答 / mRNA分解 / mRNA修飾 / サイトカイン / 自然免疫応答 / mRNA制御 / ｍRNA分解 / 免疫制御

Outline of Annual Research Achievements

1. mRNA 3’ UTRを介した免疫細胞時空間制御機構の解析
mRNA 3' UTR制御分子であるRegnase-1の機能に関する解析を行い、マウスを用いた実験からII型自然リンパ球（ILC2）に発現するRegnase-1が、ILC2の活性化や増殖を制御することで、肺線維症の増悪抑制に重要な働きをしていることを見出した。さらに、ヒト特発性肺線維症患者のILC2数とRegnase-1発現量に逆相関を認めること、血液中のILC2数が多い特発性肺線維症患者では有意に生存期間が短いことが明らかとなった（Nakatsuka et al. Euro. Respir. J. 2020）。潰瘍性大腸炎患者の解析から上皮細胞においてRegnase-1の変異が存在する事を明らかにした。特に、Regnase-1がリン酸化を受ける部位のアミノ酸に高頻度の変異を認め、この変異Regnase-1は分解に対して抵抗性であり、炎症に抑制的に働き上皮細胞の生存適応に寄与していることが示唆された（Kakiuchi et al. Nature 2020）。
また、Regnase-1の発現をその自己制御を抑制することで増加させる制御法を開発し、これがマウスマクロファージでTLR刺激に対する炎症性サイトカイン産生を抑制する事、いくつかのマウス炎症、自己免疫疾患モデルを抑制しうることを解明した。
2．コドンに隠された新たな免疫応答分子制御機構の解析
ヒトタンパク質mRNAのコドン頻度の網羅的な分析により、コドンを3番目の塩基にGまたはCを持つもの（GC3）とAまたはTを持つもの（AT3）がそれぞれ、mRNAの安定化、不安定化に関わる事が明らかとなった。この分子機構に関する解析を行い、新たな制御分子の同定に成功した。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

本研究で、3'UTRを介したmRNA制御分子の免疫制御における役割をRegnase-1の制御の観点から解析し、Regnase-1の発現を増強させる変異がヒト潰瘍性大腸炎（UC）患者腸上皮において高頻度に認められることが明らかとなり（Kakiuchi et al. Nature 2020）、Regnase-1が、肺上皮細胞において緑膿菌感染に対する自然免疫応答の制御に重要な役割を果たしていること（Mucosal Immunol 2018）や、Type II Innate Lymphoid Cell (ILC2)の活性化を制御し、マウスやヒトの肺において肺線維症の発症を抑制する機能を担っていることを見出した（Nakatsuka et al. Euro Respir J 2020）。このように、Regnase-1によるmRNA分解を介した転写後制御は、ヒト炎症性疾患や重要な役割を果たしていることを明らかにした。これは、自己免疫疾患や感染症の発症機構を解明する上で学術的に重要なものである。また、3' UTRだけでなくタンパク質コード領域のコドンバイアスによるｍRNA制御機構の解明も、その現象の報告（Hia et al. EMBO Rep 2019）以降も順調に進展しており、本研究課題は順調に進展している。

Strategy for Future Research Activity

1. mRNA 3’ UTRを介した免疫細胞時空間制御機構の解析
Regnase-1、Roquin結合分子としてBioID解析により同定した複合体構成分子群の機能解析を細胞からマウス個体レベルに展開することにより、Regnase-1やRoquin依存性mRNA分解の分子機構の全体像を明らかにしていく。また、開発中のRegnase-1制御法に関し、ヒト細胞における制御法を開発していく。
2．コドンに隠された新たな免疫応答分子制御機構の解析
スクリーニングにより同定したコドンによるmRNA制御に関わる新規分子群に関し、細胞やマウス個体レベルでノックアウトする事により、mRNAやタンパク質発現に与える影響、免疫応答に与える影響を検討していく。
3. mRNAエピトランスクリプトームを介した免疫制御機構の解明
免疫細胞の活性化に際し、m6Aメチル化に関わるZc3h13分子のRNA結合が増強することを既に見出している。この分子に関し、T細胞やマクロファージで細胞特異的遺伝子欠損マウスを作製し、その自然免疫、獲得免疫細胞分化・活性化における役割の解明を行っていく。

Assessment Rating

Interim Assessment Comments (Rating)

A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.

Research Products

• [Int'l Joint Research] ULM University(ドイツ)
• [Int'l Joint Research] MDC(ドイツ)
• [Int'l Joint Research] ULM University/MDC Berlin(ドイツ)
• [Int'l Joint Research] Stanford University/Chicago University(米国)
• [Int'l Joint Research] Strasbourg University(フランス)
• [Journal Article] Profibrotic function of pulmonary group 2 innate lymphoid cells is controlled by Regnase-1 (2020)
  • Author(s): Yoshinari Nakatsuka, Ai Yaku, Tomohiro Handa, Alexis Vandenbon, Yuki Hikichi, Yasutaka Motomura, Yutaka Suzuki, Takuya Uehata, Takashi Mino, Tohru Tsujimura, Kazuyo Moro, Osamu Takeuchi, et al.
  • Journal Title: European Respiratory Journal Volume: 57 Pages: 2000018-2000018
  • DOI: 10.1183/13993003.00018-2020
  • Peer Reviewed
• [Journal Article] Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis (2020)
  • Author(s): Kakiuchi Nobuyuki et al.
  • Journal Title: Nature. Volume: 577 Pages: 260-265
  • DOI: 10.1038/s41586-019-1856-1
  • NAID: 120006777064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The transcription factor E2A activates multiple enhancers that drive Rag expression in developing T and B cells (2020)
  • Author(s): Miyazaki Kazuko、Watanabe Hitomi、Yoshikawa Genki、Chen Kenian、Hidaka Reiko、Aitani Yuki、Osawa Kai、Takeda Rie、Ochi Yotaro、Tani-ichi Shizue、Uehata Takuya、Takeuchi Osamu、Ikuta Koichi、Ogawa Seishi、Kondoh Gen、Lin Yin C.、Ogata Hiroyuki、Miyazaki Masaki
  • Journal Title: Science Immunology, Volume: 5 Pages: 1455-1455
  • DOI: 10.1126/sciimmunol.abb1455
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Zinc Finger Protein St18 Protects against Septic Death by Inhibiting VEGF-A from Macrophages (2020)
  • Author(s): Maruyama Kenta、Kidoya Hiroyasu、Takemura Naoki、Sugisawa Erika、Takeuchi Osamu、Kondo Takeshi、Eid Mohammed Mansour Abbas、Tanaka Hiroki、Martino Mika?l M.、Takakura Nobuyuki、Takayama Yasunori、Akira Shizuo、Vandenbon Alexis、Kumagai Yutaro
  • Journal Title: Cell Rep Volume: 32 Pages: 107906-107906
  • DOI: 10.1016/j.celrep.2020.107906
  • Peer Reviewed / Open Access
• [Journal Article] The effects of codon bias and optimality on mRNA and protein regulation (2020)
  • Author(s): Fabian Hia, Osamu Takeuchi
  • Journal Title: Cellular and Molecular Life Sciences Volume: 78 Pages: 1909-1928
  • DOI: 10.1007/s00018-020-03685-7
  • Peer Reviewed
• [Journal Article] RNA Recognition and Immunity-Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms (2020)
  • Author(s): Takuya Uehata, Osamu Takeuchi
  • Journal Title: Cells Volume: 9 Pages: 1701-1701
  • DOI: 10.3390/cells9071701
  • Peer Reviewed / Open Access
• [Journal Article] Live-Cell Imaging of Protein Degradation Utilizing Designed Protein-Tag Mutant and Fluorescent Probe with Turn-Off Switch (2020)
  • Author(s): Gao J, Hori Y, Takeuchi O, Kikuchi K
  • Journal Title: Bioconjugate Chemistry Volume: 31 Pages: 577-583
  • DOI: 10.1021/acs.bioconjchem.9b00696
  • Peer Reviewed
• [Journal Article] N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation. (2019)
  • Author(s): Yamasoba D, Sato K, Ichinose T, Imamura T, Koepke L, Joas S, Reith E, Hotter D, Misawa N, Akaki K, Uehata T, Mino T, Miyamoto S, Noda T, Yamashita A, Standley DM, Kirchhoff F, Sauter D, Koyanagi Y, Takeuchi O.
  • Journal Title: Nat Microbiol. Volume: 4 Pages: 1532-1544
  • DOI: 10.1038/s41564-019-0460-3
  • NAID: 120006731123
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Translation-dependent unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs. (2019)
  • Author(s): Mino, T., Iwai, N., Endo, M., Inoue, K., Akaki, K., Hia, F., Uehata, T., Emura, T., Hidaka, K., Suzuki, Y., Standley, D. M., Okada-Hatakeyama, M., Ohno, S., Sugiyama, H., Yamashita, A., Takeuchi, O.
  • Journal Title: Nucleic Acids Research Volume: 47 Pages: 8838-8859
  • DOI: 10.1093/nar/gkz628
  • NAID: 120006708220
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Codon bias confers stability to human mRNAs (2019)
  • Author(s): Hia Fabian、Yang Sheng Fan、Shichino Yuichi、Yoshinaga Masanori、Murakawa Yasuhiro、Vandenbon Alexis、Fukao Akira、Fujiwara Toshinobu、Landthaler Markus、Natsume Tohru、Adachi Shungo、Iwasaki Shintaro、Takeuchi Osamu
  • Journal Title: EMBO reports Volume: 20
  • DOI: 10.15252/embr.201948220
  • NAID: 120006767912
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] NET-CAGE characterizes the dynamics and topology of human transcribed cis-regulatory elements (2019)
  • Author(s): Hirabayashi Shigeki、Bhagat Shruti、Matsuki Yu、Takegami Yujiro、Uehata Takuya、Kanemaru Ai、Itoh Masayoshi、Shirakawa Kotaro、Takaori-Kondo Akifumi、Takeuchi Osamu、Carninci Piero、Katayama Shintaro、Hayashizaki Yoshihide、Kere Juha、Kawaji Hideya、Murakawa Yasuhiro
  • Journal Title: Nature Genetics Volume: 51 Pages: 1369-1379
  • DOI: 10.1038/s41588-019-0485-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post‐transcriptional control of immune responses and its potential application (2019)
  • Author(s): Yoshinaga Masanori、Takeuchi Osamu
  • Journal Title: Clinical & Translational Immunology Volume: 8
  • DOI: 10.1002/cti2.1063
  • NAID: 120006784407
  • Peer Reviewed
• [Journal Article] RNA binding proteins in the control of autoimmune diseases (2019)
  • Author(s): Yoshinaga Masanori、Takeuchi Osamu
  • Journal Title: Immunological Medicine Volume: 42 Pages: 53-64
  • DOI: 10.1080/25785826.2019.1655192
  • Peer Reviewed
• [Journal Article] Hassall’s corpuscles with cellular-senescence features maintain IFNα production through neutrophils and pDC activation in the thymus (2019)
  • Author(s): Wang Jianwei、Sekai Miho、Matsui Takeshi、Fujii Yosuke、Matsumoto Mitsuru、Takeuchi Osamu、Minato Nagahiro、Hamazaki Yoko
  • Journal Title: International Immunology Volume: 31 Pages: 127-139
  • DOI: 10.1093/intimm/dxy073
  • NAID: 120007164929
  • Peer Reviewed / Open Access
• [Journal Article] N4BP1 restricts HIV-1 and its inactivation by MALT1 promotes viral reactivation (2019)
  • Author(s): Yamasoba D, Sato K, Ichinose T, Imamura T, Koepke L, Joas S, Reith E, Hotter D, Misawa N, Akaki K, Uehata T, Mino T, Miyamoto S, Noda T, Yamashita A, Standley DM, Kirchhoff F, Sauter D, Koyanagi Y, Takeuchi O.
  • Journal Title: Nature Microbiology Volume: 印刷中
  • NAID: 120006731123
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Translation of Hepatitis A Virus IRES Is Upregulated by a Hepatic Cell-Specific Factor (2018)
  • Author(s): Sadahiro Akitoshi、Fukao Akira、Kosaka Mio、Funakami Yoshinori、Takizawa Naoki、Takeuchi Osamu、Duncan Kent E.、Fujiwara Toshinobu
  • Journal Title: Front Genet. Volume: 9 Pages: 1-10
  • DOI: 10.3389/fgene.2018.00307
  • NAID: 120006534584
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Post-transcriptional regulation of immune responses by RNA binding proteins (2018)
  • Author(s): MINO Takashi、TAKEUCHI Osamu
  • Journal Title: Proc. Jpn. Acad., Ser. B Volume: 94 Issue: 6 Pages: 248-258
  • DOI: 10.2183/pjab.94.017
  • NAID: 130007395766
  • ISSN: 0386-2208, 1349-2896
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary Regnase-1 orchestrates the interplay of epithelium and adaptive immune systems to protect against pneumonia. (2018)
  • Author(s): Nakatsuka, Y., Vandenbon, A., Mino, T., Yoshinaga, M., Uehata, T., Cui, X., Sato, A., Tsujimura, T., Suzuki, Y., Sato, A., Handa, T., Chin, K., Sawa, T., Hirai, T., Takeuchi, O.
  • Journal Title: Mucosal Immunology Volume: AOP Pages: 1203-1218
  • DOI: 10.1038/s41385-018-0024-5
  • Peer Reviewed / Int'l Joint Research
• [Presentation] RNA代謝による自然免疫応答の惹起と制御 (2020)
  • Author(s): 竹内理
  • Organizer: 日本臨床免疫学会
  • Invited
• [Presentation] Regulatory mechanisms of innate immune responses (2020)
  • Author(s): Osamu Takeuchi
  • Organizer: FIMSA Immunology course-2020
  • Int'l Joint Research / Invited
• [Presentation] Immune regulation by translation-dependent mRNA decay (2020)
  • Author(s): Osamu Takeuchi
  • Organizer: MBSJ2020
  • Invited
• [Presentation] Regnase-1による免疫調節機構 (2020)
  • Author(s): 竹内理
  • Organizer: 第7回免疫セミナー
  • Invited
• [Presentation] RNA分解による免疫応答の制御機構 (2020)
  • Author(s): 竹内理
  • Organizer: 2020年度東京大学医科学研究所国際共同利用・共同研究拠点成果報告会
  • Invited
• [Presentation] Manipulation of Regnase-1 mRNA stability alleviates inflammatory responses in diseased models (2020)
  • Author(s): Tse, K.M., Cui, X., Uehata, T., Takeuchi, O
  • Organizer: MBSJ2020
  • Invited
• [Presentation] Codon Bias Confers Stability to mRNAs in Humans, The 25th Annual Meeting of the RNA Society (2020)
  • Author(s): Hia, F., Yang, S.F., Shichino, Y., Yoshinaga, M., Murakawa, Y., Vandenbon, A., Fukao, A., Fujiwara, T., Landthaler, M., Natsume, T., Adachi, S., Iwasaki, S., Takeuchi, O.
  • Organizer: RNA2020
  • Int'l Joint Research
• [Presentation] Manipulation of Regnase-1 mRNA stability alleviates inflammatory responses in diseased models (2020)
  • Author(s): Tse, K.M., Cui, X., Uehata, T., Takeuchi, O.
  • Organizer: RNA2020
  • Int'l Joint Research
• [Presentation] LYMPHOID-MYELOID CELL FATE DETERMINATION BY ENDORIBONUCLEASES REGNASE-1 AND -3 (2020)
  • Author(s): Takuya, U., Yamada, S., Miyazaki, M., Giladi, A., Vandenbon, A., Amit, I., Kawamoto, H., Takeuchi, O.
  • Organizer: 8th Annual Meeting of the International Cytokine & Interferon Society
  • Int'l Joint Research
• [Presentation] Regulation of immune responses by RNA degradation (2019)
  • Author(s): Osamu Takeuchi
  • Organizer: The 18th Awaji International Forum on Infection and Immunity
  • Int'l Joint Research / Invited
• [Presentation] Control of Immune Responses via RNA Degradation (2019)
  • Author(s): Osamu Takeuchi
  • Organizer: The Polish-Japanese Meeting on RNA
  • Int'l Joint Research / Invited
• [Presentation] Unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs. (2019)
  • Author(s): Takashi Mino, Osamu Takeuchi
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] Ribonucleases Regnase-1 and Regnase-3 have a critical role in cotrolling transcriptome biases in LMPP to ensure lymphopoiesis. (2019)
  • Author(s): Shinnosuke Yamada, Takuya Uehata, Osamu Takeuchi
  • Organizer: 第48回日本免疫学会学術集会
• [Presentation] ヒトにおけるコドンバイアスによるmRNA安定性制御 (2019)
  • Author(s): 竹内理
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] 免疫細胞を制御するRNA結合タンパク質の機能解析 (2019)
  • Author(s): 植畑拓也
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Endonucleases Regnase-1 and Regnase-3 regulate transcriptome biases to ensure lymphopoiesis. (2019)
  • Author(s): Takuya Uehata, Osamu Takeuchi
  • Organizer: CiRA 2019 International Symposium
  • Int'l Joint Research
• [Presentation] RNA分解による免疫細胞の制御機構 (2019)
  • Author(s): 竹内理
  • Organizer: 第8回さきがけ「RNAと生体機能」研究会
• [Presentation] Critical roles of endonucleases Regnase-1 and Regnase-3 in early lymphopoiesis. (2019)
  • Author(s): Takuya Uehata, Osamu Takeuchi
  • Organizer: 17th International Congress of Immunology
  • Int'l Joint Research
• [Presentation] 免疫細胞制御における翻訳とmRNA分解の連関 (2019)
  • Author(s): 竹内理
  • Organizer: 第92回日本生化学会大会
• [Presentation] Regnase-1による炎症性mRNA分解機構 (2019)
  • Author(s): 三野享史
  • Organizer: 第7 回CCR4-NOT研究会
• [Presentation] Codon Bias Confers Stability to mRNAs via ILF2 in Humans (2019)
  • Author(s): Hia, F., Takeuchi, O
  • Organizer: 第21回日本RNA学会年会
• [Presentation] RNA分解を介した免疫制御機構 (2019)
  • Author(s): 竹内理
  • Organizer: 第40回日本炎症・再生医学会
• [Presentation] dentification of a host RNA binding protein as a novel HIV-1 restriction factor. (2018)
  • Author(s): Yamasoba, D., Sato, K., Hotter, D., EReith, E., Koepke, L., Linsenmeyer, R., Standley, D.M., Sauter, D., Koyanagi, Y., and Takeuchi, O.
  • Organizer: Cold Spring Harbor Laboratory Meeting on Retroviruses
  • Int'l Joint Research
• [Presentation] The ribonuclease Regnase-1 maintains iron homeostasis via the destabilization of iron-regulatory transcripts. (2018)
  • Author(s): Yoshinaga, M., Mino, T., and Takeuchi, O.
  • Organizer: RNA2018
  • Int'l Joint Research
• [Presentation] The role of CyclinJ in modulating innate immune cells and inflammation. (2018)
  • Author(s): Chong, Y.K., Tartey, S, and Takeuchi, O.
  • Organizer: The 25th International Symposium on Molecular Cell Biology of Macrophages.
• [Presentation] Regnase-1による炎症性mRNA分解機構 (2018)
  • Author(s): 三野享史
  • Organizer: 第6回CCR4-NOT研究会
• [Presentation] 新規RNA分解酵素によるHIV-1感染制御機構の解明 (2018)
  • Author(s): 山岨大智，佐藤佳，小柳義夫，竹内理
  • Organizer: 第29回日本生体防御学会学術総会
• [Presentation] mRNA分解による免疫調節機構とその制御 (2018)
  • Author(s): 竹内理
  • Organizer: 日本核酸医薬学会第4回年会
  • Invited
• [Presentation] Posttranscriptional control of pro-inflammatory cytokine expression by Regnase-1 and Roquin (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: WCP2018
  • Int'l Joint Research / Invited
• [Presentation] 鉄代謝を制御する転写後調節機構の解明 (2018)
  • Author(s): 吉永正憲，三野享史，Bassik, M. C.，竹内理
  • Organizer: 第20回日本RNA学会年会
  • Invited
• [Presentation] SMG1はRegnase-1経路を介して炎症性mRNAを制御する (2018)
  • Author(s): 三野享史，岩井紀貴，赤木宏太朗，山下暁朗，竹内 理
  • Organizer: 第20回日本RNA学会年会
• [Presentation] A型肝炎ウイルスIRES依存的翻訳は肝臓特異的因子により活性化される (2018)
  • Author(s): 貞廣暁利，深尾亜喜良，小坂実央，滝沢直己，船上仁範，竹内理，Duncan, K.E.，藤原俊伸
  • Organizer: 第20回日本RNA学会年会
• [Presentation] Exploring the RNA Regulational Landscape via Codon Optimality. (2018)
  • Author(s): Hia, F.
  • Organizer: RNA Frontier Meeting 2018
• [Presentation] RNA分解酵素Regnase-1による鉄代謝制御機構 (2018)
  • Author(s): 竹内 理
  • Organizer: 第４２回日本鉄バイオサイエンス学会学術集会
  • Invited
• [Presentation] Post-transcriptional control of innate immune responses (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: Japan-Germany Immunology Workshop
  • Int'l Joint Research / Invited
• [Presentation] MALT1-mediated cleavage of N4BP1, an antiviral RNase, contributes to the viral reactivation in latently HIV-1 infected cells (2018)
  • Author(s): 山岨大智，佐藤佳，小柳義夫，竹内理
  • Organizer: 第66回ウイルス学会学術集会
• [Presentation] Innate immune Sensing and Regulation (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: 第66回ウイルス学会学術集会
  • Invited
• [Presentation] Regnase-1によるmRNA分解を介した免疫制御機構 (2018)
  • Author(s): 竹内理
  • Organizer: 第91回日本生化学会大会
  • Invited
• [Presentation] Regnase-1は鉄代謝関連のmRNAを分解することで鉄恒常性を維持する (2018)
  • Author(s): 吉永正憲，三野享史，竹内理
  • Organizer: 第41回日本分子生物学会年会
• [Presentation] mRNA分解を介した免疫制御機構 (2018)
  • Author(s): 竹内理
  • Organizer: 第41回日本分子生物学会年会
  • Invited
• [Presentation] MALT1によるN4BP1の分解は潜伏感染HIV-1の再活性化を促進する (2018)
  • Author(s): 山岨大智，佐藤佳，小柳義夫，竹内理
  • Organizer: 第32回日本エイズ学会学術集会・総会
  • Invited
• [Presentation] The role of CyclinJ as a Novel Regulator in Modulating Tumor-associated Macrophage (TAM). (2018)
  • Author(s): Chong, Y.K., and Takeuchi, O.
  • Organizer: The 47th Annual Meeting of the Japanese Society for Immunology
• [Presentation] Critical roles of endonucleases Regnase-1 and Regnase-3 in early lymphopoiesis (2018)
  • Author(s): Takuya Uehata, Shinnosuke Yamada, Masaki Miyazaki, Hiroshi Kawamoto, Osamu Takeuchi
  • Organizer: Keystone Symposia, Transcription and RNA Regulation in Inflammation and Immunity (B1)
  • Int'l Joint Research / Invited
• [Presentation] Critical Roles of an RNase N4BP1 in Anti-HIV-1 Host Defense and its Control by TCR Signaling (2018)
  • Author(s): Osamu Takeuchi
  • Organizer: Keystone Symposia, Transcription and RNA Regulation in Inflammation and Immunity (B1)
  • Int'l Joint Research / Invited
• [Remarks] 肺線維症における新規治療標的候補となるRNA分解酵素Regnase-1を同定
  • URL: https://www.kyoto-u.ac.jp/ja/research-news/2020-10-14-2
• [Remarks] 宿主がHIV-1感染を抑制する新たなメカニズムの解明
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190528_1.html
• [Remarks] 炎症が制御される新たなRNA分解メカニズムを解明 －新たな免疫賦活化法の開発に道筋－
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190722_2.html
• [Remarks] ヒト細胞のコドン（遺伝暗号）に隠された暗号を解明 －ヒトコドン最適化制御による治療戦略の開発へ－
  • URL: http://www.kyoto-u.ac.jp/ja/research/research_results/2019/190904_2.html
• [Patent(Industrial Property Rights)] 炎症抑制用の組成物 (2018)
  • Inventor(s): 竹内理
  • Industrial Property Rights Holder: 竹内理
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-054780
  • Filing Date: 2018