Elucidating the functions of CCL20 and CCL9 chemokines in multiple sclerosis via genome editing
Project/Area Number |
20K16499
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 51030:Pathophysiologic neuroscience-related
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Research Institution | Oita University |
Principal Investigator |
Sachi Nozomi 大分大学, 医学部, 技術専門職員 (90777468)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | ケモカイン / 多発性硬化症 / CCL20 / CCR6 / CCL9 / 病態モデルマウス / ゲノム編集マウス / CCR1 / ケモカインCCL20 / ケモカインCCL9 |
Outline of Research at the Start |
難治性自己免疫疾患の多発性硬化症の発症には、炎症性のTh17細胞や抗炎症性のTreg細胞などのヘルパーT細胞が重要な役割を果たす。これらの細胞の中枢神経系内の病巣への集積は、アストロサイトが分泌する細胞走化性因子であるケモカインによって制御されているが、その詳細は不明である。本研究は、ケモカインCCL20及びCCL9に着目し、ゲノム編集技術で独自に作製した遺伝子欠損マウスに多発性硬化症を実験的に誘発して細胞局在や病態スコアを解析し、これらケモカインの病態形成における役割を解明するものである。
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Outline of Final Research Achievements |
To elucidate the physiological role of the chemokines CCL20 and CCL9 in multiple sclerosis, inbred CCL20, CCL9, and CCR6-deficient mice were generated by genome editing and analyzed for the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which showed symptoms comparable to or more severe than those of wild-type mice. In particular, CCL20/CCR6 deficiency did not affect the infiltration of Th17 cells or Treg cells into the CNS, suggesting that CCL20/CCR6 is not necessarily required for the development of EAE and may be compensated by other chemokine signals. This study demonstrates for the first time the physiological role of CCL20, and at the same time, provides some conclusions on the long- controversial role of CCR6 in EAE.
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Academic Significance and Societal Importance of the Research Achievements |
ケモカインによる白血球遊走の理解は、ダイナミックな免疫システムの全容を捉える上で不可欠である。近年、リンパ球のホーミングや遊走に関連した分子を標的とした自己免疫疾患の治療薬の開発が進められている。例えば、α4インテグリン阻害薬が多発性硬化症や潰瘍性大腸炎の治療に用いられている。今後の自己免疫疾患の治療薬開発にケモカインによる免疫制御機構の理解が必須であると考えられるが、多発性硬化症におけるCCL20/CCR6の生理的役割を明確にした本研究成果は、ケモカインに対する洞察を深める重要な知見であり、その学術的および社会的意義は大きい。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Comprehensive lipidomics of lupus-prone mice using LC-MS/MS identifies the reduction of palmitoylethanolamide that suppresses TLR9-mediated inflammation.2022
Author(s)
Ozaki T, Kamiyama N, Saechue B, Soga Y, Gotoh R, Nakayama T, Fukuda C, Dewayani A, Chalalai T, Ariki S, Ozaka S, Sonoda A, Hirose H, Gendo Y, Noguchi K, Sachi N, Hidano S, Maeshima K, Gotoh K, Masaki T, Ishii K, Osada Y, Shibata H, Kobayashi T
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Journal Title
Genes Cells.
Volume: 27
Issue: 7
Pages: 493-504
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Protease inhibitory activity of secretory leukocyte protease inhibitor ameliorates murine experimental colitis by protecting the intestinal epithelial barrier2021
Author(s)
Ozaka S, Sonoda A, Ariki S, Kamiyama N, Hidano S, Sachi N, Ito K, Kudo Y, Minata M, Saechue B, Dewayani A, Chalalai T, Soga Y, Takahashi Y, Fukuda C, Mizukami K, Okumura R, Kayama H, Murakami K, Takeda K, Kobayashi T.
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Journal Title
Genes to Cells
Volume: 26
Issue: 10
Pages: 807-822
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Functional analysis of chemokine receptor CCR2 in a murine congenital toxoplasmosis model2022
Author(s)
Noganori Kamiyama, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Thanyakorn Chalalai, Yasuhiro Soga, Chiaki Fukuda, Yomei Kagoshima, Supanuch Ekronarongchai, Masahiro Yamamoto, Takashi Kobayashi
Organizer
第15回寄生虫感染免疫研究会
Related Report
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[Presentation] Zika virus induces Th17 cell-attracting chemokines in the central nervous system and exacerbates neurological disorders.2021
Author(s)
Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Chalalai Thanyakorn, Sotaro Ozaka, Shimpei Ariki, Chiaki Fukuda, Yasuhiro Soga, Mizuki Minata, Nozomi Sachi, Shinya Hidano, Takashi Kobayashi.
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] 大建中湯のSLPI発現増強を介した腸管保護作用の解析.2021
Author(s)
皆田美月, 小坂聡太郎, 有木晋平, 神山長慶, 佐知望美, Benjawan Saechue, Astri Dewayani, Thanyakorn Chalalai, 曽我泰裕, 福田千瑛, 水上一弘, 村上和成, 小林隆志.
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] Verification of T cell inhibitory effect of lipid mediator Oleylethanolamide2021
Author(s)
Yasuhiro Soga, Naganori Kamiyama, Takashi Ozaki, Benjawan Saechue, Astri Dewayani, Nozomi Sachi, Sotaro Ozaka, Shinpei Ariki, Thanyakorn Chalalai, Chiaki Fukuda, Takashi Kobayash
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] "Identification of a responsible amino acid in prME protein for cell entry of Zika virus using single-round infectious particles (SRIPs)"2021
Author(s)
Chiaki Fukuda, Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Chalalai Thanyakorn, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Mizuki Minata, Nozomi Sachi, Shinya Hidano, Ryosuke Suzuki,Takashi Kobayashi
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] T細胞特異的TRAF6欠損マウスを用いた腸管におけるnon-pathogenic Th17細胞に関する研究2021
Author(s)
有木晋平, 小坂聡太郎, 神山長慶, Benjawan Saechue, Astri Dewayani, Thanyakorn Chalalai, 佐知望美, 曽我泰裕, 福田千瑛, 水上一弘, 村上和成, 小林隆志
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] TRAF6 regulates Th9 cells and cytotoxic T lymphocytes in tumor immunity2021
Author(s)
Astri Dewayani, Naganori Kamiyama, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Benjawan Saechue, Yasuhiro Soga, Thanyakorn Chalalai, Chiaki Fukuda, Takashi Kobayashi
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] C.rodentium感染における樹状細胞におけるTRAF6シグナルの役割2021
Author(s)
Thanyakorn Chalala, Naganori Kamiyama, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Benjawan Saechue, Yasuhiro Soga, Astri Dewayani, Chiaki Fukuda, Takashi Kobayashi
Organizer
第44回日本分子生物学会年会
Related Report
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[Presentation] TRAF6 promotes the migration of Th17 cells into the CNS by regulating CCR6 expression in experimental autoimmune encephalomyelitis mice2020
Author(s)
Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Chalalai Thanyakorn, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Mizuki Goto, Nozomi Sachi, Shinya Hidano, Takashi Kobayashi
Organizer
第43回日本分子生物学会年会
Related Report
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[Presentation] TRAF6 Signaling in Th9 cells Regulates Anti-Tumor Immune Response2020
Author(s)
Astri Dewayani, Naganori Kamiyama, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Benjawan Saechue, Mizuki Goto, Yasuhiro Soga, Thanyakorn Chalalai, Takashi Kobayashi
Organizer
第43回日本分子生物学会年会
Related Report