Mechanisms of differentiation and homing of aberrantly glycosylated IgA producing cells in the pathogenesis of IgA nephropathy
| Project/Area Number |
18K08252
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | IgA腎症 / 粘膜免疫 / 免疫複合体 / ホーミング / Toll様受容体 / APRIL / TLR / 糖鎖異常IgA1 |
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| Outline of Final Research Achievements |
Dysregulation of mucosal immune response is involved in the pathogenesis of IgA nephropathy. However, the whereabouts of the responsible cells involved in the production of glycan abnormality IgA1 have not been identified. In present study, it was clarified that aberrantly glycosylated IgA-producing cells, which are key molecular in the pathophysiology of IgA nephropathy, are mainly desensitized and differentiated in nasopharynx-associated lymphoid tissue (NALT) using a natural onset model of IgA nephropathy. Analysis of homing receptors suggested that aberrantly glycosylated IgA-producing cells sensitized in NALT are homing into the bone marrow and differentiate to long-lived plasma cells.
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| Academic Significance and Societal Importance of the Research Achievements |
IgA腎症は世界で最も頻度の高い原発性糸球体腎炎であり、腎糸球体に糖鎖修飾異常を伴ったIgA（糖鎖異常IgA）の沈着を特徴とする。予後不良な疾患であり、指定難病に認定されている。現在、科学的根拠がないまま扁桃摘出あるいは腸管選択的作用型ステロイドを用いた治験などが進行している。本研究成果により、科学的根拠をもった適切な治療ガイドを示すことが可能である。IgA腎症の予後を改善することで透析導入を抑制し、医療費の削減を図ることが可能であると考える。
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Report
(4 results)
Research Products
(55 results)
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[Journal Article] Leukemia inhibitory factor signaling enhances production of galactose-deficient IgA1 in IgA nephropathy2020
Author(s)
Yamada K, Huang Z, Raska M, Reily C, Anderson J, Suzuki H, Kiryluk K, Gharavi AG, Julian BA, Willey CD, Novak J
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Journal Title
Kidney Dis (Basel)
Volume: 6
Issue: 3
Pages: 168-180
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Experimental evidence of pathogenic role of IgG autoantibodies in IgA nephropathy2020
Author(s)
Moldoveanu Z, Suzuki H, Reily C, Satake K, Novak L, Xu N, Huang ZQ, Knoppova B, Khan A, Hall S, Yanagawa H, Brown R, Winstead CJ, O’Quinn DB, Weinmann A, Gharavi AG, Kiryluk K, Julian BA, Weaver CT, Suzuki Y, Novak J
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Journal Title
J Autoimmune
Volume: 118
Pages: 102593-102593
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A Proliferation Inducing Ligand (APRIL) targeted antibody is a safe and effective treatment of murine IgA nephropathy2019
Author(s)
Myette JR, Kano T, Suzuki H, Sloan SE, Szretter KJ, Ramakrishnan B, Adari H, Deotale KD, Engler F, Shriver Z, Wollacott AM, Suzuki Y, Pereira BJG
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Journal Title
Kidney Int
Volume: 19
Issue: 1
Pages: 30174-30177
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Critical role for mucosal-associated invariant T cells as regulators and therapeutic targets in systemic lupus erythematosus2019
Author(s)
Murayama G, Chiba A, Suzuki H, Nomura A, Mizuno T, Kuga T, Nakamura S, Amano H, Hirose S, Yamaji K, Suzuki Y, Tamura N, Miyake S
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Journal Title
Frontiers in Immunology
Volume: 29
Pages: 2681-2681
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The dual endothelin type A receptor(ETAR) and angiotensin II type 1 receptor (AT1R) antagonist, sparsentan, protects against the development of albuminuria and glomerulosclerosis in the gddY mouse model of lgA nephropathy2020
Author(s)
Nagasawa H, Suzuki H, Celia J, Ueda S, Fukao Y, Nakayama M, Otsuka T, Kai L, Rodko K, Suzuki Y
Organizer
The ASN (American Society of Nephrology) 53th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] GWAS-follow-up study identified abnormal LIF signaling network involving STAT1 and Src family protein-tyrosine kinases in IgA1-secreting cells from patients with IgA nephropathy2018
Author(s)
Yamada K, Huang ZQ, Raska M, Reily C, Anderson JC, Suzuki H, Kiryluk K, Gharavi AG, Julian BA, Willey CD, Novak J
Organizer
51th American Society of Nephrology Meeting
Related Report
Int'l Joint Research
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