Development of the molecular targeted therapy for allergic dermatitis

• Project/Area Number: 25293091
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Tsukuba
• Principal Investigator: SHIBUYA Kazuko 筑波大学, 医学医療系, 准教授 (00302406)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 免疫系受容体 / アレルギー性皮膚炎 / costimulatory 分子 / ヘルパーT細胞分化 / 分子標的療法 / 免疫学 / 皮膚 / ヘルパーT細胞

Outline of Final Research Achievements

Although Th1 and Th2 cells are known to be involved in allergic inflammatory diseases, the molecular mechanisms underlying their differentiation are incompletely understood. Here, we identified CD155 as a costimulatory molecule on CD4+ T cells. CD155-mediated signaling induced Th1 development. Mice treated with anti-CD155 antibody exhibited attenuated Th1-type contact hypersensitivity. Thus, CD155 plays an important regulatory role in helper T-cell differentiation and allergic diseases.

Research Products

• [Journal Article] Increased soluble CD155 in the serum of cancer patients (2016)
  • Author(s): Iguchi-Manaka A, Okumura G, Kojima H, Cho Y, Hirochika R, Bando H, Sato T, Yoshikawa H, Hara H, Shibuya A, Shibuya K.
  • Journal Title: PLoS One Volume: 11(4) Issue: 4 Pages: 1-12
  • DOI: 10.1371/journal.pone.0152982
  • NAID: 120007135543
  • Peer Reviewed / Open Access
• [Journal Article] Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces (2016)
  • Author(s): Nakahashi-Oda C, Udayanga KGS, Nakamura Y, Nakazawa Y, Miki H, Iino S, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Journal Title: Nature Immunol, 17(4):441-453, 2016 Volume: 17 Issue: 4 Pages: 441-453
  • DOI: 10.1038/ni.3345
  • Peer Reviewed / Open Access
• [Journal Article] Expression of DNAM-1 (CD226) on inflammatory monocytes (2015)
  • Author(s): Vo AV, Takenaka E, Shibuya A, Shibuya K.
  • Journal Title: Mol Immunol Volume: 69 Pages: 70-76
  • DOI: 10.1016/j.molimm.2015.11.009
  • NAID: 120007129692
  • Peer Reviewed / Open Access
• [Journal Article] IgM-Dependent Phagocytosis in Microglia Is Mediated by Complement Receptor 3, Not Fcα/μ Receptor (2015)
  • Author(s): Weinstein JR, Quan Y, Hanson JF, Colonna L, Iorga M, Honda S, Shibuya K, Shibuya A, Elkon KB, Möller T.
  • Journal Title: J Immunol Volume: 195(11) Issue: 11 Pages: 5309-5317
  • DOI: 10.4049/jimmunol.1401195
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CD155 (PVR/Necl5) Mediates a Costimulatory Signal in CD4+ T Cells and Regulates Allergic Inflammation (2015)
  • Author(s): 4.Yamashita--Kanemaru Y, Takahashi Y, Wang Y, Tahara-Hanaoka S, Honda S, Bernhardt G, Shibuya A, Shibuya K.
  • Journal Title: J Immunol, 194(12):5644-5653, 2015 Volume: 194 Issue: 12 Pages: 5644-5653
  • DOI: 10.4049/jimmunol.1401942
  • Peer Reviewed / Open Access
• [Journal Article] CD155 (PVR/Necl5) mediates a costimulatory signal in CD4+ T cells and regulates allergic inflammations. (2015)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Tahara-Hanaoka S, Honda S, Bernhardt G, Shibuya A, Shibuya K.
  • Journal Title: J Immunol Volume: in press
  • Peer Reviewed
• [Journal Article] Increased CD11b+ Gr-1+ cell population in the placenta after infection with Toxoplasma gondii. (2015)
  • Author(s): Takeshima K, Sato K, Nabekura T, Nagamune K, Hamada H, Yoshikawa H, Shibuya A, Shibuya K.
  • Journal Title: Microbiol. immunol Volume: 59 Issue: 2 Pages: 95-98
  • DOI: 10.1111/1348-0421.12225
  • NAID: 120007130301
  • Peer Reviewed / Open Access
• [Journal Article] Increased CD112 expression in methylcholanthrene-induced tumors in CD155-deficient mice. (2014)
  • Author(s): Nagumo Y, Iguchi-Manaka A, Shibuya A, Shibuya K.
  • Journal Title: PLoS ONE Volume: 9(11) Issue: 11 Pages: e112415-e112415
  • DOI: 10.1371/journal.pone.0112415
  • NAID: 120007136536
  • Peer Reviewed / Open Access
• [Journal Article] Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated infammatory monocyte migration (2014)
  • Author(s): Naoya T otsuka, Yun-Gi Kim, Kazumasa Kanemaru, Kouta Niizuma, Eiji Umemoto, Kei Nagai, Satoko T ahara-Hanaoka, Chigusa Nakahasi-Oda, Shin-ichiro Honda, Masayuki Miyasaka, Kazuko Shibuya & Akira Shibuya
  • Journal Title: Nature Communications Volume: 5:4710 Issue: 1 Pages: 4710-4710
  • DOI: 10.1038/ncomms5710
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy. (2014)
  • Author(s): Satake K, Shimizu Y, Sasaki Y, Yanagawa H, Suzuki H, Suzuki Y, Horikoshi S, Honda S, Shibuya K, Shibuya A, Tomino Y.
  • Journal Title: BMC Nephrology Volume: 15:89 Issue: 1 Pages: 89-89
  • DOI: 10.1186/1471-2369-15-89
  • Peer Reviewed / Open Access
• [Journal Article] Establishment and Characterization of a Novel Anti-DNAM-1 Monoclonal Antibody (2013)
  • Author(s): Yamashita Y, Abe F, Hirochika R, Tahara-Hanaoka S, Shibuya A, Shibuya K.
  • Journal Title: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Volume: 32(1) Issue: 1 Pages: 60-64
  • DOI: 10.1089/mab.2012.0083
  • Peer Reviewed
• [Journal Article] CD226 interaction with CD155 impacts on retention and negative selection of CD8 positive thymocytes as well as T cell differentiation to follicular helper cells in Peyer's Patches. (2013)
  • Author(s): Danisch S et. al.
  • Journal Title: Immunobiology Volume: 218 Issue: 2 Pages: 152-158
  • DOI: 10.1016/j.imbio.2012.02.010
  • Peer Reviewed
• [Presentation] Expression of DNAM-1 (CD226) on inflammatory monocytes The 55th Midwinter Conference of Immunologists (2016)
  • Author(s): Vo AV, Takenaka E, Shibuya A, Shibuya K
  • Organizer: The 55th Midwinter Conference of Immunologists
  • Place of Presentation: Asilomar Conference Grounds, Pacific Grove California, (USA)
  • Year and Date: 2016-01-23
  • Int'l Joint Research
• [Presentation] Increased soluble CD155 in patients with various cancers (2015)
  • Author(s): Iguchi-Manaka A, Shibuya A, Shibuya K
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] Involvement of DNAM-1 (CD226) expressed on small peritoneal macrophages in antigen presentation (2015)
  • Author(s): Takenaka E, Vo AV, Shibuya A, Shibuya K
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] evelopment of a novel method for isolation of follicular dendritic cells (2015)
  • Author(s): Sato K, Honda S, Shibuya K, Shibuya A.
  • Organizer: 第44回日本免疫学会総会・学術集会
  • Place of Presentation: 札幌コンベンションセンター（札幌）
  • Year and Date: 2015-11-18
• [Presentation] The role of DNAM-1 and CD155 in tumor immunity and escape (2015)
  • Author(s): Shibuya K, Iguchi-Manaka A, Kojima H, Cho Y, Hirochika R, Shibuya A.
  • Organizer: International Symposium on Immune Regulation
  • Place of Presentation: Oarai Park Hotel, Oarai (Japan)
  • Year and Date: 2015-10-29
  • Int'l Joint Research
• [Presentation] Apoptotic epithelial cells control regulatory T cell expansion (2015)
  • Author(s): Nakahashi-Oda C, Udayanga K G S, Nakamura Y, Nakazawa Y, Totsuka N, Miki H, Iino S, Tahara-Hanaoka S, Honda S, Shibuya K, Shibuya A.
  • Organizer: International Symposium on Immune Regulation
  • Place of Presentation: Oarai Park Hotel, Oarai (Japan)
  • Year and Date: 2015-10-29
  • Int'l Joint Research
• [Presentation] Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signaling International Symposium on Immune Regulation (2015)
  • Author(s): Honda S, Sato K, Totsuka N, Fujiyama S, Fujimoto M, Miyake K, Nakahashi-Oda C, Tahara-Hanaoka S, Honda S, Shibuya K, Shibuya A.
  • Organizer: International Symposium on Immune Regulation
  • Place of Presentation: Oarai Park Hotel, Oarai (Japan)
  • Year and Date: 2015-10-29
  • Int'l Joint Research
• [Presentation] Increased soluble CD155 in the serum of cancer patients (2015)
  • Author(s): Iguchi-Manaka A, Hiroshi Kojima, Cho Y, Shibuya A, Shibuya K
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場（名古屋）
  • Year and Date: 2015-10-08
• [Presentation] 癌患者血清における可溶型CD155の上昇 (2015)
  • Author(s): 井口研子、渋谷彰、渋谷和子
  • Organizer: 第7回血液疾患免疫療法研究会学術集会
  • Place of Presentation: 東京大学 伊藤国際学術研究センター（東京）
  • Year and Date: 2015-09-26
• [Presentation] 免疫監視と免疫逃避におけるポリオウイルスレセプターの役割 (2015)
  • Author(s): 渋谷 和子
  • Organizer: 東北大学加齢医学研究所セミナー
  • Place of Presentation: 東北大学加齢医学研究所（仙台）
  • Year and Date: 2015-03-23
  • Invited
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection. (2015)
  • Author(s): 阿部 史枝、渋谷 和子、渋谷 彰
  • Organizer: 第3回筑波大学・東京理科大学生命医科学研究所合同リトリート
  • Place of Presentation: 東京理科大学セミナーハウス（野田）
  • Year and Date: 2015-03-20
• [Presentation] Soluble CD155 is involved in the escape from tumor immunity. (2015)
  • Author(s): 井口 研子、渋谷 彰、渋谷 和子
  • Organizer: 第3回筑波大学・東京理科大学生命医科学研究所合同リトリート
  • Place of Presentation: 東京理科大学セミナーハウス（野田）
  • Year and Date: 2015-03-20
• [Presentation] Soluble CD155 is involved in the escape from tumor immunity. (2015)
  • Author(s): Iguchi-Manaka A, Shibuya A, Shibuya K.
  • Organizer: 第5回新学術発がんスパイラル国際シンポジウム
  • Place of Presentation: 神戸ポートピアホテル（神戸）
  • Year and Date: 2015-02-26
• [Presentation] DNAM-1 (CD226) plays an important role in antigen presentation by small peritoneal macrophages. (2015)
  • Author(s): Takenaka E, Shibuya A, Shibuya K.
  • Organizer: 第5回新学術発がんスパイラル国際シンポジウム
  • Place of Presentation: 神戸ポートピアホテル（神戸）
  • Year and Date: 2015-02-26
• [Presentation] DNAM-1 (CD226) plays an important role in antigen presentation by small peritoneal macrophages. (2014)
  • Author(s): Takenaka E, Shibuya A, Shibuya K.
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-11
• [Presentation] Soluble CD155 is involved in the escape from tumor immunity. (2014)
  • Author(s): Iguchi-Manaka A, Shibuya A, Shibuya K.
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10
• [Presentation] Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration. (2014)
  • Author(s): Totsuka N, Kim YG, Kanemaru K, Niizuma K, Umemoto E, Nagai K, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Miyasaka M, Shibuya K, Shibuya A.
  • Organizer: 第43 回日本免疫学会総会・学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-12-10
• [Presentation] CD155 regulates regulatory T cell population and attenuates acute graft-versus-host disease. (2014)
  • Author(s): Kanaya M, Shibuya K, Abe F, Teshima T, Shibuya A.
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪）
  • Year and Date: 2014-10-31
• [Presentation] 免疫システムの人為的制御と疾患の克服 (2014)
  • Author(s): 渋谷 和子
  • Organizer: 第46回日本医学教育学会大会
  • Place of Presentation: 和歌山県立医科大学（和歌山）
  • Year and Date: 2014-07-18
• [Presentation] 可溶型ポリオウイルスレセプター（CD155)によるがん免疫逃避 (2014)
  • Author(s): 渋谷 和子
  • Organizer: 第26回千葉基礎・臨床免疫セミナー
  • Place of Presentation: 千葉大亥鼻イノベーションプラザ（千葉）
  • Year and Date: 2014-05-22
  • Invited
• [Presentation] 腫瘍免役逃避機構における可溶型CD155の役割 (2014)
  • Author(s): 井口 研子、清松 裕子、池田 達彦、坂東 裕子、渋谷 彰、渋谷 和子、原 尚人
  • Organizer: 第114回日本外科学会定期学術集会
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] Involvement of soluble CD155 in cancer immune escape. (2013)
  • Author(s): Iguchi A, Shibuya A, Shibuya K
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Fca/mR (CD351) regulates inflammatory responses of marginal zone B cells against experimental septic shock. (2013)
  • Author(s): Honda S, Yoshizawa Y, Sato K, Fujimoto M, Nakahashi-Oda C, Tahara-Hanaoka S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Involvement of CD300a in the pathogenesis of DSS-induced colitis. (2013)
  • Author(s): Totsuka N, Kim YG, Tahara-Hanaoka S, Nakahashi-Oda C, Honda S, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Critical role of DNAM-1 in acute and chronic allograft rejection. (2013)
  • Author(s): Abe F, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] A co-stimulatory molecule CD155 on CD4+ T Cells regulates allergic reactions by induction of interferon-γ-dependent th1 development. (2013)
  • Author(s): Yamashita Y, Takahashi Y, Wang Y, Shibuya A, Shibuya K.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] Soluble DNAX accessory molecule-1 (sDNAM-1) is a novel predictive biomarker for acute graft-versus-host disease. (2013)
  • Author(s): Kanaya M, Shibuya K, Shibuya A.
  • Organizer: 第42回日本免疫学会総会・学術集会
  • Place of Presentation: 幕張メッセ（千葉）
• [Presentation] CD155 is a co-stimulatory molecule involved in Th1 development. International Symposium Immune Regulation by Immunoreceptors.
  • Author(s): Yamashita Y, Takahashi Y, Abe F, Shibuya A, Shibuya K.
  • Organizer: International Symposium Immune Regulation by Immunoreceptors.
  • Place of Presentation: University of Tsukuba.（つくば）
• [Presentation] The role of an activating receptor, DNAM-1 (CD226), on small peritoneal macrophages (SPMs).
  • Author(s): Takenaka E, Shibuya A, Shibuya K.
  • Organizer: International Symposium Immune Regulation by Immunoreceptors.
  • Place of Presentation: University of Tsukuba.（つくば）
• [Book] 実験医学別冊 最強のステップUPシリーズ 直伝！フローサイトメトリー 面白いほど使いこなせる！ (2014)
  • Author(s): 金丸 由美、渋谷 和子
  • Publisher: 羊土社
• [Book] 公益財団法人金原一郎記念医学医療振興財団「生体の科学」 (2013)
  • Author(s): 竹中 江里、渋谷 和子、渋谷 彰
  • Publisher: 医学書院
• [Remarks] 免疫学研究室ホームページ
  • URL: http://immuno-tsukuba.com/index.html
• [Remarks] つくばリポジトリ
  • URL: https://tsukuba.repo.nii.ac.jp/index.php?action=pages_view_main&active_action=repository_view_main_item_snippet&index_id=987&pn=1&count=20&order=7&lang=japanese&page_id=13&block_id=83
• [Remarks] TRIOS
  • URL: http://trios.tsukuba.ac.jp/researcher/0000001639
• [Patent(Industrial Property Rights)] 可溶型CD155タンパク質を用いた癌の検出方法 (2015)
  • Inventor(s): 渋谷彰、渋谷和子、井口研子
  • Industrial Property Rights Holder: 渋谷彰、渋谷和子、井口研子
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-01-26
  • Acquisition Date: 2015-07-27
• [Patent(Industrial Property Rights)] 可溶型CD155タンパク質を用いた癌の検出方法 (2015)
  • Inventor(s): 渋谷 彰、渋谷 和子、井口 研子
  • Industrial Property Rights Holder: 渋谷 彰、渋谷 和子、井口 研子
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-01-26
• [Patent(Industrial Property Rights)] 免疫疾患に対する医薬組成物 (2014)
  • Inventor(s): 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Holder: 渋谷 和子、渋谷 彰、山下 由美
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-13