Physiological role of TRAF6, CCL20 and SLPI in the regulation of intestinal homeostasis
Project/Area Number |
17K08889
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Immunology
|
Research Institution | Oita University |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
花田 礼子 大分大学, 医学部, 教授 (00343707)
神山 長慶 大分大学, 医学部, 助教 (50756830)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | TRAF6 / CCL20 / SLPI / 腸炎 / パイエル板 / 腸管バリア機能 / ILC3 / Th17細胞 |
Outline of Final Research Achievements |
Previous studies have suggested that signals mediated by the adapter molecule TRAF6 in T cells and intestinal epithelial cells function to maintain homeostasis of intestinal tissues. Therefore, we focused on chemokine CCL20 and secretory leukocyte peptidase inhibitor (SLPI), whose expression is regulated by TRAF6 signal in intestinal epithelial cells, and analyzed the intestinal tissues in mice deficient for these molecules. SLPI-deficient mice showed a severe phenotype of DSS-induced colitis compared to that in wild-type mice. Peyer's patches from CCL20-deficient mice were smaller, showing a lower number of Lin(-), ROR-γt(+) and CCR6(+) LTi-like ILC3 than those from WT animals suggesting that CCL20 regulates the migration of ILC3 into the Peyer's patches.
|
Academic Significance and Societal Importance of the Research Achievements |
TRAF6シグナルによって腸上皮細胞から誘導されるSLPIが、腸管組織における恒常性の維持に重要であることが遺伝子改変マウスの解析から明らかになった。すなわち、SLPIはプロテアーゼ阻害活性により過剰な炎症反応で生じる組織損傷に対して腸管組織を保護していることが示唆された。また、ケモカインCCL20の遺伝子欠損マウスはパイエル板の形成不全とその中へのILC3の遊走障害、さらには腸内細菌叢の偏重が認められたことから、CCL20も腸管組織における恒常性の維持に重要であることが示された。腸管組織の恒常性維持に働く分子の機能解明により、今後のヒト腸疾患の予防法・治療法の開発に貢献するものと考えられる。
|
Report
(4 results)
Research Products
(57 results)
-
[Journal Article] CLP1 acts as the main RNA kinase in mice2020
Author(s)
Fujinami H, Shiraishi H, Hada K, Inoue M, Morisaki I, Higa R, Shin T, Kobayashi T, Hanada R, Penninger JM, Mimata H, Hanada T.
-
Journal Title
Biochem Biophys Res Commun.
Volume: 525
Issue: 1
Pages: 129-134
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
[Journal Article] Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling.2018
Author(s)
Kanaya T, Sakakibara S, Jinnohara T, Hachisuka M, Tachibana N, Hidano S, Kobayashi T, Kimura S, Iwanaga T, Nakagawa T, Katsuno T, Kato N, Akiyama T, Sato T, Williams IR, Ohno H.
-
Journal Title
J Exp Med.
Volume: 5;215(2)
Issue: 2
Pages: 501-519
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
[Journal Article] Ribavirin inhibits Zika virus (ZIKV) replication inハvitro and suppresses viremia in ZIKV- infected STAT1-deficient mice.2017
Author(s)
Kamiyama N, Soma R, Hidano S, Watanabe K, Umekita H, Fukuda C, Noguchi K, Gendo Y, Ozaki T, Sonoda A, Sachi N, Runtuwene LR, Miura Y, Matsubara E, Tajima S, Takasaki T, Eshita Y, Kobayashi T.
-
Journal Title
Antiviral Res.
Volume: 146
Pages: 1-11
DOI
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
[Presentation] "Zika virus African strain has higher entry ability to host cell than Asian strain, and exacerbates EAE"2019
Author(s)
Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Mizuki Goto, Ryosuke Suzuki ,Takashi Kobayashi
Organizer
第42回日本分子生物学会年会
Related Report
-
[Presentation] ゲノム編集マウスを用いたケモカインCCL20の腸管組織における生理的機能の解析2019
Author(s)
Nozomi Sachi, Chiaki Fukuda, Shinya Hidano, Naganori Kamiyama, Benjawan Saechue, Sotaro Ozaka, Astri Dewayani, Shimpei Ariki, Yasuhiro Soga, Mizuki Goto, Takashi Kobayashi
Organizer
第42回日本分子生物学会年会
Related Report
-
-
[Presentation] 白癬菌増殖抑制効果を有するわさびの機能分子の探索2019
Author(s)
Mizuki Goto, Haruna Hirose, Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Takashi Kobayashi
Organizer
第42回日本分子生物学会年会
Related Report
-
-
-
-
-
-
-
[Presentation] アニサキス感染におけるIgE誘導機序の解析2019
Author(s)
小林隆志, 飛彈野真也, 水上 一弘, 財津 純可, 草野 耀永, 伊藤 秀幸, Astri Dewayani, 小坂 聡太郎, Benjawan Saechue, 佐知望美, 神山長慶, 村上 和成
Organizer
第88回日本寄生虫学会大会
Related Report
-
-
-
-
-
[Presentation] Development of a rapid and simple reverse transcription loop-mediated isothermal amplification for Chikungunya virus2018
Author(s)
Benjawan Saechue, Naganori Kamiyama, Shinya Hidano, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki, Akira Sonoda, Haruna Hirise, Nozomi Sachi, Sotaro Ozaka, Takashi Kobayashi,
Organizer
41回日本分子生物学会年会
Related Report
-
[Presentation] アフリカ株とアジア株SRIPsを用いた、ジカウイルスの宿主細胞侵入効率の解析2018
Author(s)
神山長慶, 渡辺 景, Benjawan Saechue, 飛彈野真也, 野口香緒里, 玄同淑子, 尾崎貴士, 園田光, 広瀬 晴奈, 小坂 聡太郎, 佐知望美, 鈴木 亮介, 小林隆志
Organizer
41回日本分子生物学会年会
Related Report
-
-
-
-
-
-
-
[Presentation] T細胞特異的TRAF6欠損マウスは実験的自己免疫性脳脊髄炎の発症が抑制される2018
Author(s)
Naganori Kamiyama, Benjawan Saechu, Shinya Hidano, Kei Watanabe, Hidekazu Matsuoka, Kaori Noguchi, Yoshiko Gendo, Takashi Ozaki, Akira Sonoda, Nozomi Sachi, Yuki Eshita, Takashi Kobayashi
Organizer
第4回病因研究会別府シンポジウム
Related Report
-
-
-
-
-
-
-
[Presentation] 新規脂質メディエーターのOEA及びPEAは、Toll様受容体9(TLR9)刺激による樹状細胞とB細胞の活性化を抑制する2017
Author(s)
尾崎貴士, 後藤 亮, 園田光, 広瀬 晴奈, 玄同淑子, 野口香緒里, 神山長慶, 飛彈野真也, 石井宏治, 柴田洋孝, 小林 隆志
Organizer
第8回 癌・炎症と抗酸化研究会(CIA研究会)
Related Report
-
[Presentation] Ribavirin inhibits Zika virus (ZIKV) replication in vitro and suppresses viremia in ZIKV-infected STAT1-deficient mice2017
Author(s)
Naganori Kamiyama, Ryusuke Soma, Shinya Hidano, Benjawan Saechue, Nozomi Sachi, Kaori Noguchi, Takashi Ozaki, Akira Sonoda, Yoshiko Gendo, Yuki Eshita, and Takashi Kobayashi,
Organizer
2017年度生命科学系学会合同年次大会(日本分子生物学会)
Related Report
-
[Presentation] Inhibition of TLR9-induced dendritic cell activation and pro-inflammatory cytokine production by Oleoylethanolamide, whose level is reduced in MRL/lpr mice2017
Author(s)
尾崎貴士, 園田光, 玄同淑子, 野口香緒里, 佐知望美, 神山長慶, 飛彈野真也, 石井宏治, 柴田洋孝, 小林隆志
Organizer
2017年度生命科学系学会合同年次大会(日本分子生物学会)
Related Report
-
-
-
-
-