Development of diagnostic techniques specific for Sjogren's syndrome by estrogen-related molecules

• Project/Area Number: 15K15676
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: ISHIMARU Naozumi 徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (60314879)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Akiko 徳島大学, 大学院医歯薬学研究部, 助教 (70452646)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 自己免疫疾患 / シェーグレン症候群 / エストロゲン / 性ホルモン / 診断 / 唾液腺 / 唾液 / 涙腺 / 涙液

Outline of Final Research Achievements

It is well known that many autoimmune diseases including SS occur during postmenopausal stage in female, suggesting that estrogens largely influence immune system. The aim of this study is developing diagnostic techniques for SS by applying estrogen-related molecules which play key roles in the onset or development of SS. Retinoblastoma-associated protein 48 (RbAp48) was a key marker for pathological diagnosis of SS using histological specimens of SS patients. In addition, it is possible that insulin-growth factor-binding protein 5 (IGFBP5) and CXCL10 are also crucial molecules as estrogen-related molecules for diagnosis using sera and saliva of SS patients. Our results in this study will be linked with development of new diagnostic techniques for autoimmune diseases.

Research Products

• [Journal Article] Unique Phenotypes and Functions of Follicular Helper T Cell and Regulatory T Cell in Sjogren's Syndrome. (2017)
  • Author(s): Saito M, Otsuka K, Ushio A, Yamada A, Arakaki R, Kudo Y, Ishimaru N.
  • Journal Title: Curr Rheumatol Rev. Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Crucial roles of macrophages in the pathogenesis of autoimmune disease. (2017)
  • Author(s): Ushio A, Arakaki R, Yamada A, Saito M, Tsunematsu T, Kudo Y, Ishimaru N.
  • Journal Title: World J Immunol. Volume: 7 Issue: 1 Pages: 1-8
  • DOI: 10.5411/wji.v7.i1.1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Deal role of Fs/FasL-mediated signal in peripheral immune tolerance (2017)
  • Author(s): Yamada A, Arakaki R, Saito M, Kudo Y, Ishimaru N
  • Journal Title: Front in Immunol Volume: 印刷中
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The nuclear receptor AhR controls bone homeostasis by regulating osteoclast differentiation via the RANKL/c-Fos signaling axis. (2016)
  • Author(s): Izawa T, Arakaki R, Mori H, Tsunematsu T, Kudo Y, Tanaka E, Ishimaru N.
  • Journal Title: J Immunol Volume: 197（12） Pages: 4639-4650
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Oral environment and cancer. (2016)
  • Author(s): Kudo Y, Tada H, Fujiwara N, Tada Y, Tsunematsu T, Miyake Y, Ishimaru N.
  • Journal Title: Genes Environ. Volume: 1 Issue: 1 Pages: 38-13
  • DOI: 10.1186/s41021-016-0042-z
  • NAID: 120006937648
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Human odontogenic epithelial cells derived from epithelial rests of Malassez possess stem cell properties. (2016)
  • Author(s): Tsunematsu T, Fujiwara N, Yoshida M, Takayama Y, Kujiraoka S, Qi G, Kitagawa M, Kondo T, Yamada A, Arakaki R, Miyauchi M, Ogawa I, Abiko Y, Nikawa H, Murakami S, Takata T, Ishimaru N, Kudo Y.
  • Journal Title: Lab Invest. Volume: 96(10) Issue: 10 Pages: 1063-1075
  • DOI: 10.1038/labinvest.2016.85
  • NAID: 120006718349
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PARP6 acts as a tumor suppressor via dowregulating Survivin expression in colorectal cancer. (2016)
  • Author(s): Qi G, Kudo Y, Tang B, Liu T, Jin S, Liu J, Zuo X, Mi S, Shao W, Ma X, Tsunematsu T, Ishimaru N, Zeng S, Tatsuka M, Shimamoto F.
  • Journal Title: Oncotarget. Volume: 印刷中 Issue: 14 Pages: 18812-18824
  • DOI: 10.18632/oncotarget.7712
  • Peer Reviewed
• [Journal Article] Intraoral ultrasonography of tongue mass lesions. (2016)
  • Author(s): Sugawara C, Takahashi A, Kawano F, Kudo Y, Ishimaru N, Miyamoto Y.
  • Journal Title: Dentomaxillofac Radiol. Volume: 45(5) Issue: 5 Pages: 20150362-20150362
  • DOI: 10.1259/dmfr.20150362
  • NAID: 120006487438
  • Peer Reviewed
• [Journal Article] Acceleration of tumor growth due to dysfunction in Ma macrophages and enhanced angiogenesis in an animal model of autoimmune disease. (2016)
  • Author(s): Kondo T, Tsunematsu T, Yamada A, Arakaki R, Saito M, Otsuka K, Kujiraoka S, Ushio A, Kurosawa M, Kudo Y, Ishimaru N.
  • Journal Title: Lab Invest Volume: 96 Issue: 4 Pages: 468-480
  • DOI: 10.1038/labinvest.2015.166
  • Peer Reviewed / Open Access
• [Journal Article] Molecular mechanisms of nickel allergy. (2016)
  • Author(s): Saito M, Arakaki R, Yamada A, Tsunematsu T, Kudo Y, Ishimaru N.
  • Journal Title: Int J Mol Sci Volume: 17 Issue: 2 Pages: 202-202
  • DOI: 10.3390/ijms17020202
  • NAID: 120006374403
  • Peer Reviewed / Open Access
• [Journal Article] Role of regulatory T cell in inflammatory bowel disease. (2016)
  • Author(s): Yamada A, Arakaki R, Tsunematsu T, Kudo Y, Ishimaru N.
  • Journal Title: World J Gastroenterol. Volume: 22 Issue: 7 Pages: 2195-2205
  • DOI: 10.3748/wjg.v22.i7.2195
  • Peer Reviewed / Open Access
• [Journal Article] The non-canonical role of Aurora-A in DNA replication. Front Oncol (2015)
  • Author(s): Tsunematsu T, Arakaki R, Yamada A, Ishimaru N, Kudo Y
  • Journal Title: Front Oncol Volume: 96 Pages: 468-480
  • DOI: 10.3389/fonc.2015.00187
  • Peer Reviewed / Open Access
• [Journal Article] Impaired Expansion of Regulatory T Cells in A Neonatal Thymectomy-Induced Autoimmune Mouse Model. (2015)
  • Author(s): Yamada A, Ushio A, Arakaki R, Tsunematsu T, Kudo Y, Hayashi Y, Ishimaru N.
  • Journal Title: Am J Pathol Volume: 185 Issue: 11 Pages: 2886-2897
  • DOI: 10.1016/j.ajpath.2015.07.007
  • NAID: 120006711357
  • Peer Reviewed / Open Access
• [Journal Article] Intrathymic B cell licensing for Aire expression and T cell tolerance induction. (2015)
  • Author(s): Yamano T, Nedjic J, Hinteberger M, Koser S, Pinto S, Gerdes N, Lutgens E, Ishimaru N, Busslinger M, Brors B, Kyewski B, Klein L.
  • Journal Title: Immunity Volume: 42 Issue: 6 Pages: 1048-1061
  • DOI: 10.1016/j.immuni.2015.05.013
  • Peer Reviewed
• [Journal Article] Protection from diet-induced obesity and insulin resistance in mice lacking CCL19-CCR7 signaling. (2015)
  • Author(s): Sano T, Iwashita M, Nagayasu S, Yamashita A, Shinjo T, Hashikata A, Asano T, Kushiyama A, Ishimaru N, Takahama Y, Nishimura F
  • Journal Title: Obesity Volume: 23 Issue: 7 Pages: 1460-1471
  • DOI: 10.1002/oby.21127
  • Peer Reviewed / Open Access
• [Journal Article] Possible involvement of palmitate in pathogensis of periodontitis. (2015)
  • Author(s): Shikama Y, Kudo Y, Ishimaru N, Funaki M.
  • Journal Title: J Cell Physiol. Volume: 230 Issue: 12 Pages: 298-298
  • DOI: 10.1002/jcp.25029
  • Peer Reviewed
• [Presentation] Analysis of follicular helper T cells in a mouse model for Sjogren’s syndrome (2016)
  • Author(s): Kunihiro Otsuka, Masako Saito, Mie Kurosawa, Aya Ushio, Akiko Yamada, Rieko Arakaki, Yasusei Kudo, Naozumi Ishimaru
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県・宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Immunological and toxicological effect of multi-wall carbon nanotubes by whole body inhalation exposure in B6 mice. (2016)
  • Author(s): Yamada Koichi, Arakaki Rieko, Ushio Aya, Kurosawa Emi, Otsuka Kunihiro, Saito Masako, Tsunematsu Takaaki, Yamada Akiko, Kudo Yasusei, Ishimaru Naozumi
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県・宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Analysis of macrophages in the pathogenesis of a murine model for Sjogren's syndrome. (2016)
  • Author(s): Aya Ushio, Rieko Arakaki, Masako Saito, Akiko Yamada, Kunihiro Otsuka, Mie Kurosawa, Satoko Kujiraoka, Yasusei Kudo, and Naozumi Ishimaru
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県・宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] Toxicological effect of peritoneal exposure to multi-walled carbon nanotubes on immune system (2016)
  • Author(s): Masako Saito, Kunihiro Otsuka, Rieko Arakaki, Koichi Yamada, Naozumi Ishimaru
  • Organizer: 第45回日本免疫学会総会
  • Place of Presentation: 沖縄コンベンションセンター（沖縄県・宜野湾市）
  • Year and Date: 2016-12-05
• [Presentation] 口腔扁平上皮癌におけるPeriostinスプライシングバリアントの新たな役割 (2016)
  • Author(s): 梅田 将旭, 常松 貴明, 齋藤雅子, 山田 安希子, 新垣 理恵子, 工藤 保誠, 石丸 直澄
  • Organizer: 第27回日本臨床口腔病理学会総会・学術大会
  • Place of Presentation: 広島大学（広島県・広島市）
  • Year and Date: 2016-08-10
• [Presentation] シェーグレン症候群モデルマウスの病態形成におけるマクロファージの役割 (2016)
  • Author(s): 牛尾綾、新垣理恵子、大塚邦紘、齋藤雅子、山田安希子、鯨岡聡子、工藤保誠、常松貴明、近藤智之、石丸直澄
  • Organizer: 第 105 回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-12
• [Presentation] シェーグレン症候群モデルマウスにおける濾胞ヘルパーT細胞の網羅的解析 (2016)
  • Author(s): 大塚邦紘、齋藤雅子、山田安希子、牛尾綾、鯨岡聡子、工藤保誠、常松貴明、近藤智之、新垣理恵子、石丸直澄
  • Organizer: 第 105 回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-12
• [Presentation] 顎骨中心性明細胞性腫瘍からの細胞株の樹立とその性状 (2016)
  • Author(s): 鯨岡 聡子, 工藤 保誠, 常松 貴明, 近藤 智之, 牛尾 綾, 大塚 邦紘, 山田 安希子, 新垣 理恵子, 石丸 直澄
  • Organizer: 第 105 回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-12
• [Presentation] 全身吸入暴露による多層化カーボンナノチューブの免疫システムへの影響 (2016)
  • Author(s): 新垣 理恵子, 常松 貴明, 山田 安希子, 齋藤 雅子, 工藤 保誠, 石丸 直澄
  • Organizer: 第 105 回日本病理学会総会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-05-12
• [Presentation] シェーグレン症候群患者におけるセファランチンの作用機序の解明 (2016)
  • Author(s): 山ノ井 朋子, 青田 桂子, 高野 栄之, 可児 耕一, 松本 文博, 桃田 幸弘, 高瀬 奈緒, 宮本 由貴, 石丸 直澄, 東 雅之
  • Organizer: 第70回日本口腔科学会学術集会
  • Place of Presentation: 福岡国際会議場（福岡県・福岡市）
  • Year and Date: 2016-04-15
• [Presentation] Migratory activety of memory T cells in aly/aly mice. (2015)
  • Author(s): Kurosawa M, Yamada A, Arakaki R, Saito M, Tsunematsu T, Kudo Y, Ishimaru N
  • 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（北海道札幌市）
  • Year and Date: 2015-12-18
• [Presentation] Analysis of function of macrophages in murine models of Sjogren’s syndrome. (2015)
  • Author(s): Arakaki R, Kurosawa M, Otsuka K, Yamada A, Saito M, Tsunematsu T, Kudo Y, Ishimaru N.
  • 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（北海道札幌市）
  • Year and Date: 2015-12-18
• [Presentation] Biological effect of multi-walled carbon nanotubes on immune system. (2015)
  • Author(s): Saito M, Arakakai R, Otsuka K, Yamada K, Kudo Y, Ishimaru N.
  • 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（北海道札幌市）
  • Year and Date: 2015-12-18
• [Presentation] Molecular Pathogenesis of Autoimmunity~Sjogren’s Syndrome~ (2015)
  • Author(s): Ishimaru N
  • Organizer: Academy of Immunology and Microbiology Series Seminar Special Symposium
  • Place of Presentation: Pohang（Korea）
  • Year and Date: 2015-10-28
  • Int'l Joint Research / Invited
• [Presentation] Molecular Pathogenesis of Sjogren’s Syndrome. (2015)
  • Author(s): Ishimaru N
  • Organizer: 7th Meeting of Asian Society of Oral and Maxillofacial Pathology
  • Place of Presentation: Taipei（China)
  • Year and Date: 2015-10-17
  • Int'l Joint Research / Invited
• [Presentation] 染色体パッセンジャー複合体タンパク質Borealinのユビキチン分解とその癌化への関与 (2015)
  • Author(s): 常松 貴明, 工藤 保誠, 近藤 智之, 牛尾 綾, , 鯨岡 聡子, 山田 安希子, 新垣 理恵子, 石丸 直澄
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] 自己免疫疾患モデルを用いた腫瘍増殖制御機構の解明 (2015)
  • Author(s): 近藤智之、常松貴明、鯨岡聡子、牛尾綾、山田安希子、新垣理恵子、工藤保誠、石丸直澄
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] 口腔癌細胞におけるペリオスチンのスプライシングバリアントの発現とその意義 (2015)
  • Author(s): 鯨岡聡子、工藤保誠、常松貴明、近藤智之、牛尾綾、山田安希子、新垣理恵子、石丸直澄
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] 自己免疫疾患モデルマウスを利用した多層化カーボンナノチューブの免疫システムへの影響 (2015)
  • Author(s): 新垣理恵子、常松貴明、山田安希子、工藤保誠、菅野純、石丸直澄
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] 顎骨中心性粘表皮癌細胞株の樹立とその性状 (2015)
  • Author(s): 工藤保誠、常松貴明、鯨岡聡子、近藤智之、牛尾綾、山田安希子、新垣理恵子、石丸直澄
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30
• [Presentation] Analysis of macrophages in the pathogenesis of a murine model for Sjogren's syndorome. (2015)
  • Author(s): 牛尾綾、新垣理恵子、近藤智之、鯨岡聡子、常松貴明、山田安希子、工藤保誠、石丸直澄
  • Organizer: 日本病理学会
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-04-30