Immunologic function of podocytes in lupus nephritis

• Project/Area Number: 26461467
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nagasaki University
• Principal Investigator: ICHINOSE Kunihiro 長崎大学, 医歯薬学総合研究科(医学系), 講師 (60437895)
• Co-Investigator(Kenkyū-buntansha): 中村 英樹 長崎大学, 病院(医学系), 講師 (10437832) ; 岩本 直樹 長崎大学, 医歯薬学総合研究科(医学系), 助教 (80437897)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: ループス腎炎 / 全身性エリテマトーデス / ポドサイト / CaMKIV / CD86 / 自己免疫性疾患

Outline of Final Research Achievements

We found that exposure of podocytes to IgG resulted in entry of IgG into the cytoplasm. DNA microarray studies of podocytes exposed to LN IgG revealed that genes that are related to the activation of immune cells or podocyte damage were upregulated.
LN IgG enters podocytes and upregulates CaMKIV followed by increased expression of genes known to be linked to podocyte damage and T cell activation. Targeted inhibition of CaMKIV in podocytes may prove of clinical use in patients with LN.

Research Products

• [Journal Article] 【全身性エリテマトーデス:病態解明の進歩】 神経精神SLE (2017)
  • Author(s): 一瀬邦弘
  • Journal Title: 炎症と免疫 Volume: 25 Pages: 133-138
• [Journal Article] SLEの中枢神経病変 (2017)
  • Author(s): 一瀬邦弘
  • Journal Title: リウマチ科 Volume: 57 Pages: 1-11
• [Journal Article] IgG4-Related Disease With an Aortoduodenal Fistula After Abdominal Aortic Aneurysm Repair. (2016)
  • Author(s): Ichinose K, Araki S, Takatani A, Tanaka T, Kawakami A.
  • Journal Title: Arthritis Rheumatol. Volume: 68 Issue: 9 Pages: 2256-2256
  • DOI: 10.1002/art.39777
  • Peer Reviewed
• [Journal Article] Lupus Nephritis IgG Induction of Calcium/Calmodulin-Dependent Protein Kinase IV Expression in Podocytes and Alteration of Their Function. (2016)
  • Author(s): Ichinose K, Ushigusa T, Nishino A, Nakashima Y, Suzuki T, Horai Y, Koga T, Kawashiri SY, Iwamoto N, Tamai M, Arima K, Nakamura H, Obata Y, Yamamoto K, Origuchi T, Nishino T, Kawakami A, Tsokos GC.
  • Journal Title: Arthritis Rheumatol. Volume: 68 Issue: 4 Pages: 944-952
  • DOI: 10.1002/art.39499
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus. (2016)
  • Author(s): Ichinose K, Arima K, Umeda M, Fukui S, Nishino A, Nakashima Y, Suzuki T, Horai Y, Koga T, Kawashiri SY, Iwamoto N, Fujikawa K, Aramaki T, Tamai M, Nakamura H, Sato S, Origuchi T, Kawakami A.
  • Journal Title: Cytokine. Volume: 79 Pages: 31-37
  • DOI: 10.1016/j.cyto.2015.12.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Soluble α-klotho is a potential biomarker associated with neuropsychiatric systemic lupus erythematosus. (2016)
  • Author(s): Ushigusa T, Ichinose K, Sato S, Michitsuji T, Shimizu T, Umeda M, Fukui S, Nishino A, Nakashima Y, Koga T, Kawashiri SY, Iwamoto N, Hirai Y, Tamai M, Nakamura H, Origuchi T, Kawakami A.
  • Journal Title: Clin Immunol. Volume: 165 Pages: 29-34
  • DOI: 10.1016/j.clim.2016.03.001
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ループス腎炎の疾患標的分子と機能解析 (2016)
  • Author(s): 一瀬邦弘
  • Journal Title: アレルギーの臨床 Volume: 36 Pages: 446-452
• [Journal Article] Proteomic profiling of antigens in circulating immune complexes associated with each of seven autoimmune diseases. (2015)
  • Author(s): Ohyama K, Baba M, Tamai M, Aibara N, Ichinose K, Kishikawa N, Kawakami A, Kuroda N.
  • Journal Title: Clin Biochem. Volume: 48 Issue: 3 Pages: 181-185
  • DOI: 10.1016/j.clinbiochem.2014.11.008
  • NAID: 120006986232
  • Peer Reviewed
• [Journal Article] Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases. (2014)
  • Author(s): chinose K, Arima K, Ushigusa T, Nishino A, Nakashima Y, Suzuki T, Horai Y, Nakajima H, Kawashiri SY, Iwamoto N, Tamai M, Nakamura H, Origuchi T, Motomura M, Kawakami A.
  • Journal Title: Clin Immunol. Volume: 157 Issue: 2 Pages: 114-120
  • DOI: 10.1016/j.clim.2015.01.010
  • NAID: 120006987160
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Combination of MRI-detcted bone marrow oedema with 2010 rheumatoid arthritis classification criteria improves the diagnostic probability early rheumatoid arthritis. (2014)
  • Author(s): Tamai M, Kita J, Nakashima Y, Suzuki T, Horai Y, Okada A, Koga T, Kawashiri S, Iwamoto N, Ichinose K, Arima K, Yama-saki S, Nakamura H, Origuchi T, Uetani M,Fukushima A, Aoyagi K, Kawakami A.
  • Journal Title: Annals of Rheumatic Diseases Volume: 73 Issue: 12 Pages: 2219-20
  • DOI: 10.1136/annrheumdis-2013-205074
  • Peer Reviewed / Open Access
• [Presentation] Evaluation of Soluble α-Klotho in Neuropsychiatric Systemic Lupus Erythematosus (2016)
  • Author(s): Ichinose K, Ushigusa T, Kawakami A
  • Organizer: The 60th Annual General Assembly and Scientific Meeting of the Japan Collage of Rheumatology
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] Anti-Suprabasin Antibody: Identification of a Novel Antibody for neuropsychiatric systemic lupus erythematosus (2016)
  • Author(s): Ichinose K, Ohyama K, Kawakami A
  • Organizer: The 60th Annual General Assembly and Scientific Meeting of the Japan Collage of Rheumatology
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
  • Year and Date: 2016-04-21
  • Int'l Joint Research
• [Presentation] 老化抑制遺伝子α-Klothoの中枢神経ループスにおける役割 (2015)
  • Author(s): 一瀬邦弘、牛草健、佐藤俊太朗、中嶋秀樹、本村政勝、川上純
  • Organizer: 第30回臨床リウマチ学会
  • Place of Presentation: 神戸国際会議場(兵庫県・神戸市)
  • Year and Date: 2015-11-21
• [Presentation] Evaluation of Soluble a-Klotho in Neuropsychiatric Systemic Lupus Erythematosus (2015)
  • Author(s): Kunihiro Ichinose, Takeshi Ushigusa, Masataka Umeda, Tomohiro Koga, Atsushi Kawakami, Shuntaro Sato
  • Organizer: 80th American College of Rheumatology(ACR) Annual Meeting
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2015-11-06
  • Int'l Joint Research
• [Presentation] 可溶性α-KlothoのNPSLEにおける意義についての検討 (2015)
  • Author(s): 一瀬邦弘、牛草健、佐藤俊太朗、中嶋秀樹、本村政勝、川上純
  • Organizer: 第43回 日本臨床免疫学会
  • Place of Presentation: 神戸国際会議場(兵庫県・神戸市)
  • Year and Date: 2015-10-22
• [Presentation] Evaluation of Soluble α-Klotho in Neuropsychiatric Systemic Lupus Erythematosus (2015)
  • Author(s): Takeshi Ushigusa, Kunihiro Ichinose, Shuntaro Sato, Atsushi Kawakami
  • Organizer: 16th Annual European Congress of Rheumatology - European League Against Rheumatism
  • Place of Presentation: Rome, Italy
  • Year and Date: 2015-06-10
  • Int'l Joint Research
• [Presentation] マルチプレックスアッセイを用いた中枢神経ループスの治療反応予測因子の検討 (2015)
  • Author(s): 一瀬邦弘、、有馬和彦、梅田雅孝、福井翔一、西野文子、中島好一、鈴木貴久、 寶來吉朗、古賀智裕、川尻真也、岩本直樹、平井康子、玉井慎美、中村英樹、折口智樹、川上純
  • Organizer: 第59回 日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] 可溶性α-KlothoのNPSLEにおける意義についての検討 (2015)
  • Author(s): 牛草健、一瀬邦弘、辻創介、梅田雅孝、福井翔一、西野文子、中島好一、鈴木貴久、寶來吉朗、川尻真也、岩本直樹、有馬和彦、玉井慎美、中村英樹、折口智樹、川上純
  • Organizer: 第59回 日本リウマチ学会総会・学術集会
  • Place of Presentation: 名古屋国際会議場(愛知県・名古屋市)
  • Year and Date: 2015-04-23
• [Presentation] Predictors of Therapeutic Outcomes in Patients with Neuropsychiatric Systemic Lupus Erythematosus (2014)
  • Author(s): Kunihiro Ichinose, Takeshi Ushigusa, Yoshikazu Nakashima, Takahisa Suzuki, Yoshiro Horai, Shin-ya Kawashiri, Naoki Iwamoto, Mami Tamai, Kazuhiko Arima, Hideki Nakamura, Tomoki Origuchi and Atsushi Kawakami
  • Organizer: ACR 2014
  • Place of Presentation: USA､Boston
  • Year and Date: 2014-11-18
• [Presentation] 全身性エリテマトーデスにおけるCaMKIVの役割 (2014)
  • Author(s): 一瀬邦弘, 古賀智裕, George C. Tsokos, 川上 純
  • Organizer: 第42回 日本臨床免疫学会
  • Place of Presentation: 東京;京王プラザホテル
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] ループス腎炎におけるCD86を介したCalcium/calmodulin dependent kinase protein type IVのpodocyte機能に対する影響 (2014)
  • Author(s): 一瀬邦弘, 牛草健, 川上純
  • Organizer: 第57回 日本腎臓学会学術総会
  • Place of Presentation: 横浜;パシフィコ横浜
  • Year and Date: 2014-07-04
• [Presentation] Role of calcium/calmodulin-dependent kinase type IV in podocyte function in lupus nephritis (2014)
  • Author(s): Kunihiro Ichinose, Takeshi Ushigusa, Tomohiro Koga, George C.Tsokos, Atsushi Kawakami
  • Organizer: EULAR 2014
  • Place of Presentation: France, Paris
  • Year and Date: 2014-06-12
• [Presentation] ループス腎炎におけるCalcium/calmodulin dependent kinase protein type IV のポドサイト機能に対する影響（第２報) (2014)
  • Author(s): 一瀬邦弘, 牛草健, 古賀智裕, George C. Tsokos, 川上 純
  • Organizer: 第58回日本リウマチ学会
  • Place of Presentation: 東京：グランドプリンスホテル新高輪 国際館パミール
  • Year and Date: 2014-04-26
• [Presentation] 当院における中枢神経ループスの 治療反応因子の検討 (2014)
  • Author(s): 一瀬邦弘, 牛草健, 高谷亜由子, 西野文子, 中島好一, 鈴木貴久, 寶來吉朗, 川尻真也, 岩本直樹, 有馬和彦, 玉井慎美, 中村英樹, 折口智樹, 川上 純
  • Organizer: 第58回日本リウマチ学会
  • Place of Presentation: 東京：グランドプリンスホテル新高輪 国際館パミール
  • Year and Date: 2014-04-25
• [Book] 全身性エリテマトーデス 診断と治療のABC 118 (2016)
  • Author(s): 一瀬邦弘、川上純
  • Total Pages: 254
  • Publisher: 最新医学社
• [Remarks] 長崎大学病院第一内科HP～リウマチ・膠原病グループ
  • URL: http://www.med.nagasaki-u.ac.jp/intmed-1/group/rheuma.html