Analysis of tissue macrophage development and its role in vivo

• Project/Area Number: 24590584
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: Kohyama Masako 大阪大学, 微生物病研究所, 助教 (40598885)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 組織マクロファージ / 分化 / Development

Outline of Final Research Achievements

Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor SPI-C is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. We found that Spic regulated the development of bone marrow macrophages (BMM) and that Spic expression was induced by heme. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor BACH1. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insights into iron homeositasis. Hmox1 (HO-1) is the enzyme that catabolizes free heme into biliverdin, iron, and CO. To analyze the function of RPM in malaria parasite clearance, we infected HO-1 conditional KO mice that lack RPM. Through the analysis of this cKO mice, we found unexpected role of RPM in parasite clearance.

Research Products

• [Journal Article] Monocyte infiltration into obese and fibrilized tissues is regulated by PILRα. (2016)
  • Author(s): Kohyama M, Matsuoka S, Shida K, Sugihara F, Aoshi T, Kishida K, Ishii KJ, Arase H.
  • Journal Title: Eur J Immunol. Volume: in press Pages: in press
  • DOI: 10.1002/eji.201545897.
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals. (2016)
  • Author(s): Bednarski JJ, Pandey R, Schulte E, White LS, Chen BR, Sandoval GJ, Kohyama M, Haldar M, Nickless A, Trott A, Cheng G, Murphy KM, Bassing CH, Payton JE, Sleckman BP.
  • Journal Title: J Exp Med. Volume: 213 Pages: 209-223
  • DOI: 10.1084/jem.20151048.
  • 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: Sialic Acids on Varicella-Zoster Virus Glycoprotein B Are Required for Cell-Cell Fusion. Volume: 290 Pages: 19833-19843
  • DOI: 10.1074/jbc.M114.635508.
  • Peer Reviewed
• [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: in press Pages: in press
  • 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, Arase H.
  • Journal Title: Int. Immunol. Volume: in press Pages: in press
  • DOI: 10.1093/intimm/dxv004
  • Peer Reviewed / Acknowledgement Compliant
• [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 Pages: 513-522
  • DOI: 10.1111/1348-0421.12180.
  • Peer Reviewed
• [Journal Article] Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria. (2014)
  • Author(s): Zhao H, Aoshi T, Kawai S, Mori Y, Konishi A, Ozkan M, Fujita Y, Haseda Y, Shimizu M, Kohyama M, Kobiyama K, Eto K, Nabekura J, Horii T, Ishino T, Yuda M, Hemmi H, Kaisho T, Akira S, Kinoshita M, Tohyama K, Yoshioka Y, Ishii KJ, Coban C.
  • Journal Title: Cell Host Microbe. Volume: 15 Pages: 551-563
  • DOI: 10.1016/j.chom.2014.04.008.
  • Peer Reviewed
• [Journal Article] Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages (2014)
  • Author(s): Haldar M, Kohyama M, So AY, Kc W, Wu X, Briseno CG, Satpathy AT, Kretzer NM, Arase H, Rajasekaran NS, Wang L, Egawa T, Igarashi K, Baltimore D, Murphy TL, Murphy KM.
  • Journal Title: Cell Volume: 156 Pages: 1223-1234
  • DOI: 10.1016/j.cell.2014.01.069.
  • Peer Reviewed
• [Journal Article] Autoantibodies to IgG/HLA-DR complexes are 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., L. Lanier, L., and Arase, H.
  • Journal Title: Proc. Natl. Acad. Sci. USA. Volume: 111 Pages: 3787-3792
  • DOI: 10.1073/pnas.1401105111
  • Peer Reviewed
• [Journal Article] Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules. (2013)
  • Author(s): Jiang, Y., Arase, N., Kohyama, M., Hirayasu, K., Suenaga, T., Jin, H., Matsumoto, M., Shida, K., L. Lanier, L., Saito, T. and Arase, H.
  • Journal Title: Int. Immunol. Volume: 25 Pages: 235-246
  • DOI: 10.1093/intimm/dxs155.
  • Peer Reviewed
• [Presentation] Myeloperoxidase/HLA classII complex 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 – 2015-11-20
• [Presentation] PILRα negatively regulates monocyte infiltration into the skin (2015)
  • Author(s): Kohyama Masako, Matsuoka Sumiko, Arase Noriko, 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 – 2015-11-20
• [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 – 2015-11-20
• [Presentation] 食餌鉄依存的な腸管CX3CR1high制御性ミエロイド細胞維持機構 (2015)
  • Author(s): 香山尚子, 香山雅子, 竹田潔
  • 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 – 2015-10-24
• [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 – 2015-10-24
• [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] PILRα negatively regulates size of adipose tissue by controlling monocyte mobility (2014)
  • Author(s): Kohyama Masako, Kishida Kazuki, 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] 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
• [Presentation] Rheumatoid factor binding to IgG heavy chain presented on HLA-DR is associated with Rheumatoid Arthritis susceptibility
  • Author(s): Jin Hui, Arase Noriko, Kohayama Masako, Saito Fumiji, Hirayasu Kouyuki, Matsumoto Maki, Shida Kyoko, Suenaga Tadahiro, Saito Takashi, Katayama Ichiro, Lanier Lewis L., Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] β2-glycoprotein I presented on MHC class II molecules are recognized by autoantibodies in antiphospholipid syndrome
  • Author(s): Tanimura Kenji, Suenaga Tadahiro, Jin Hui, Hirayasu Kouyuki, Arase Noriko, Kohayama Masako, Ebina Yasuhiko, Yasuda Shinsuke, Horita Tetsuya, Katayama Ichiro, Atsumi Tatsuya, Yamada Hideo, Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] PILRα negatively regulates DSS induced experimental colitis
  • Author(s): Kishida Kazuki, Kohyama Masako, Kurashima Yosuke, Wang Jing, Hirayasu Kouyuki, Suenaga Tadahiro, Kiyono Hiroshi, Kunisawa Jun, Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] PILRα negatively regulates monocyte mobility
  • Author(s): Kohyama Masako, Wang Jing Kishida Kazuki, Arase Hisashi
  • Organizer: 第42回日本免疫学会学術集会
  • Place of Presentation: 幕張メッセ（千葉市）
• [Presentation] Transport of misfolded ER proteins to the cell surface by MHC class II molecules
  • Author(s): Jiang, Y., Arase, N., Kohyama, M., Hirayasu, K., Suenaga, T., Jin, H., Matsumoto, M., Shida, K., L. Lanier, L., Saito, T. and Arase, H.
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸国際会議場（兵庫県）
• [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/
• [Remarks] 大阪大学微生物病研究所免疫化学分野
  • URL: http://immchem.biken.osaka-u.ac.jp/