Functional and genetic diversity of the activating receptor to recognize microbially cleaved antibody

• Project/Area Number: 26870334
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology; Human genetics
• Research Institution: Osaka University
• Principal Investigator: Hirayasu Kohyuki 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (30585170)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 細菌感染 / Bacteria / Immunoglobulin / 活性化レセプター / プロテアーゼ / LILR / 病原性微生物 / immunoglobulin / 抗体 / 免疫逃避 / 生体防御 / 免疫レセプター

Outline of Final Research Achievements

In this study, a comprehensive search for interaction between pathogens and host immune receptors was performed. In this process, it was found that microbial pathogens have evolved to acquire antibody-cleaving proteases in order to escape from the host immune system of antibody recognition. Moreover, it was also found that an orphan activating immune receptor, LILRA2, recognizes these microbially disrupted antibody in order to counteract the microbial immune evasion strategy.

Research Products

• [Int'l Joint Research] ワシントン大学医学部(米国)
• [Journal Article] LILRA2 is an innate immune sensor for microbially cleaved immunoglobulins. (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nagai H, Nakamura Y, Katayama I, Colonna M, Arase H.
  • Journal Title: Nature Microbiology Volume: - Issue: 6 Pages: 1-7
  • DOI: 10.1038/nmicrobiol.2016.54
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Functional and genetic diversity of leukocyte immunoglobulin-like receptor and implication for disease associations. (2015)
  • Author(s): Hirayasu K, Arase H.
  • Journal Title: J Hum Genet. Volume: 60 Issue: 11 Pages: 703-708
  • DOI: 10.1038/jhg.2015.64
  • NAID: 40020655165
  • Peer Reviewed
• [Journal Article] Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion. (2015)
  • Author(s): Suenaga T, Matsumoto M, Arisawa F, Kohyama M, Hirayasu K, Mori Y, Arase H.
  • Journal Title: J Biol Chem. Volume: 290 Issue: 32 Pages: 19833-19843
  • DOI: 10.1074/jbc.m114.635508
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] β2-glycoprotein I/ HLA class II complexes are novel autoantigens in antiphospholipid syndrome. (2015)
  • Author(s): Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H.
  • Journal Title: Blood Volume: 125 Issue: 18 Pages: 2835-2844
  • DOI: 10.1182/blood-2014-08-593624
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Negative regulation of DSS-induced experimental colitis by PILRα. (2015)
  • Author(s): Kishida, K., Kohyama, M., Kurashima, Y., Kogure, Y., Wang, J., Hirayasu, K., Suenaga, T., Kiyono, H., Kunisawa, J. and Arase, H.
  • Journal Title: Int. Immunol. Volume: - Issue: 6 Pages: 307-314
  • DOI: 10.1093/intimm/dxv004
  • Peer Reviewed / Open Access
• [Journal Article] Engineering large viral DNA genomes using the CRISPR-Cas9 system. (2014)
  • Author(s): Suenaga T, Kohyama M, Hirayasu K, Arase H.
  • Journal Title: Microbiol Immunol. Volume: 58（9） Issue: 9 Pages: 513-522
  • DOI: 10.1111/1348-0421.12180
  • NAID: 40020207309
  • Peer Reviewed
• [Journal Article] A motif in LILRB2 critical for Angptl2 binding and activation. (2014)
  • Author(s): Deng M, Lu Z, Zheng J, Wan X, Chen X, Hirayasu K, Sun H, Lam Y, Chen L, Wang Q, Song C, Huang N, Gao GF, Jiang Y, Arase H, Zhang CC.
  • Journal Title: Blood. Volume: 124(6) Issue: 6 Pages: 924-935
  • DOI: 10.1182/blood-2014-01-549162
  • Peer Reviewed
• [Presentation] Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2 (2016)
  • Author(s): Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, ToshifumiYamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubori, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna, Hisashi Arase
  • Organizer: 第45日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄）
  • Year and Date: 2016-12-05
• [Presentation] Induction of autoantibody by neo-self TSH receptor / MHC class II complexes (2016)
  • Author(s): Hui Jin, Noriko Arase, Sumiko Matsuoka, Kouyuki Hirayasu, Masako Kohyama, Tadahiro Suenaga, Takehiko Sasazuki and Hisashi Arase
  • Organizer: 第45日本免疫学会学術集会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄）
  • Year and Date: 2016-12-05
• [Presentation] 細菌の抗体免疫逃避を検出する新たな免疫システム (2016)
  • Author(s): 平安恒幸
  • Organizer: 第69回日本細菌学会関西支部総会・学術講演会
  • Place of Presentation: 大阪市立大学 田中記念館（大阪）
  • Year and Date: 2016-11-19
  • Invited
• [Presentation] HLA クラス I 認識受容体群 LILR の新展開 - 病原微生物によって壊された抗体を認識 する生体防御機構 - (2016)
  • Author(s): 平安 恒幸, 齋藤 史路, 末永 忠広, 信田 京子, 荒瀬 規子, 及川 敬太, 山岡 俊文, 室田 浩之, 知花 博治, 中川 一路, 久堀 智子, 永井 宏樹, 中丸 裕爾, 片山 一朗, Marco Colonna, 荒瀬 尚
  • Organizer: 第25回日本組織適合性学会大会
  • Place of Presentation: 北海道大学（北海道）
  • Year and Date: 2016-10-22
• [Presentation] Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2 (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nakagawa I, Kubori T, Nagai H, Nakamaru Y, Katayama I, Colonna M, Arase H
  • Organizer: 16th Annual Meeting of the Society for Natural Immunity
  • Place of Presentation: Taormina, Italy
  • Year and Date: 2016-10-02
  • Int'l Joint Research
• [Presentation] Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2 (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nakagawa I, Kubori T, Nagai H, Nakamaru Y, Katayama I, Colonna M, Arase H
  • Organizer: 15th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Away Island, Japan
  • Year and Date: 2016-09-06
  • Int'l Joint Research
• [Presentation] Functional analysis of sialic acids on varicella-zoster virus glycoprotein B (2015)
  • Author(s): Tadahiro Suenaga, Maki Katsumoto, Fuminori Arisawa, Masako Kohyama, Kouyuki, Hirayasu, Yasuko Mori, Hisashi Arase
  • Organizer: 第63回日本ウイルス学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡）
  • Year and Date: 2015-11-22
• [Presentation] DIR is an innate immune sensor for microbially cleaved immunoglobulins. (2015)
  • Author(s): Hirayasu, K., Saito, F., Suenaga, T., Shida, K., Arase, N., Oikawa, K., Yamaoka, T., Murota, H., Chibana, H., Nakagawa, I., Kubori, T., Nagai, H., Nakamaru, Y., Katayama, I., Colonna, M., Arase, H.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in ANCA-associated vasculitis (2015)
  • Author(s): Hiwa Ryosuke, Ohmura Koichiro, Arase Noriko, Jin Hui, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Saito Fumiji, Iwatani Hirotsugu, Atsumi Tatsuya, Terao Chikashi, Mimori Tsuneyo, Arase Hisashi
  • Organizer: 第44日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] MHC class II molecules expose autoantibody epitopes on autoantigens (2015)
  • Author(s): Jin Hui, Arase Noriko, Matsuoka Sumiko, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Sasazuki Takehiko, Arase Hisashi
  • Organizer: 第44日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道）
  • Year and Date: 2015-11-18
• [Presentation] MPO/HLA classⅡ複合体は顕微鏡的多発血管炎における自己抗体の標的である (2015)
  • Author(s): 日和良介, 大村浩一郎, 荒瀬規子, 金暉, 平安恒幸, 香山雅子, 末永忠広, 齋藤史路, 岩谷博次, 渥美達也, 寺尾知可史, 三森経世, 荒瀬尚
  • Organizer: 第43回日本臨床免疫学会総会
  • Place of Presentation: 神戸国際会議場(兵庫）
  • Year and Date: 2015-10-22
• [Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in microscopic polyangiitis. (2014)
  • Author(s): Hiwa Ryosuke, Ohmura Koichiro, Arase Noriko, Jin Hui, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Matsuoka Sumiko, Iwatani Hirotsugu, Atsumi Tatsuya, Terao Chikashi, Mimori Tsuneyo, Arase Hisashi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] MHC class II-restricted recognition of self-antigen/MHC class II complexes by autoantibodies (2014)
  • Author(s): Jin Hui, Arase Noriko, Matsuoka Sumiko, Hirayasu Kouyuki, Kohayama Masako, Suenaga Tadahiro, Nakamaru Yuji, Imatani Yoshinori, Katayama Ichiro, Arase Hisashi
  • Organizer: 第43回日本免疫学会学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Immune sensing system for bacterially degraded immunoglobulin via activating receptor DIR (2014)
  • Author(s): Kouyuki Hirayasu, Fumiji Saito, Hiroki Nagai, Kyoko Shida, Noriko Arase, Yasuhiko Horiguchi, Yuji Nakamaru, Ichiro Katayama, Hisashi Arase
  • Organizer: 第13回あわじしま感染症・免疫フォーラム
  • Place of Presentation: 奈良県新公会堂（奈良市）
  • Year and Date: 2014-09-23 – 2014-09-26
• [Presentation] Autoantibodies in Rheumatoid Arthritis Specifically Recognize IgG Heavy Chain Complexed with HLA-DR, Which is Strongly Associated with Rheumatoid Arthritis Susceptibility. (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H.
  • Organizer: The 15th Annual European Congress of Rheumatology EULAR 2014
  • Place of Presentation: Paris(France)
  • Year and Date: 2014-06-11 – 2014-06-14
• [Presentation] MHCクラスⅡ分子によって細胞外へ輸送された細胞内ミスフォールド蛋白質が自己抗体の標的分子である (2014)
  • Author(s): 金暉、荒瀬規子、平安恒幸、香山雅子、末永忠広、松岡須美子、斉藤隆、Lewis L. Lanier、荒瀬尚
  • Organizer: 第24回Kyoto T cell Conference
  • Place of Presentation: 京都大学(京都市)
  • Year and Date: 2014-05-16 – 2014-05-17
• [Book] KIR遺伝子とHLA遺伝子の共進化（週刊 医学のあゆみ 「麻酔と脳障害」） (2014)
  • Author(s): 平安恒幸
  • Publisher: 医歯薬出版株式会社
• [Remarks] 大阪大学免疫学フロンティア研究センター免疫化学研究室ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp
• [Remarks] 免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp
• [Remarks] 免疫化学分野ホームページ
  • URL: http://immchem.biken.osaka-u.ac.jp/