A novel therapeutic strategy targeting IL-9 for endometriosis that regulate proliferation, inflammation, and immunity
| Project/Area Number |
21K20995
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0906:Surgery related to the biological and sensory functions and related fields
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
Tarumi Yosuke 京都府立医科大学, 医学部附属病院, 専攻医 (90912288)
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| Project Period (FY) |
2021-08-30 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 子宮内膜症 / interleukin-9 / 免疫応答 / 免疫 / ヘルパーT細胞 / IL-9 |
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| Outline of Research at the Start |
子宮内膜症の病態には炎症や免疫反応が関与するとされてきたが、そのメカニズムは十分に解明されていない。我々はこれまでにIL-9陽性ヘルパーT細胞が子宮内膜症患者の腹水中に多く存在し、IL-9が病巣局所の細胞増殖や炎症誘導促進に関与していることを明らかにしてきた。IL-9はマクロファージの貪食能低下やTh17細胞の分化誘導を引き起こすことが知られているが、IL-9のこれらの作用は子宮内膜症の免疫応答と一致している。本研究ではIL-9が及ぼす炎症・免疫制御機構を明らかにし、IL-9およびその受容体を標的とした増殖・炎症・免疫を制御しうる包括的な子宮内膜症治療アプローチを確立させる。
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| Outline of Final Research Achievements |
Endometriosis is defined as the presence of endometrium-like lesions growing outside the uterus. The aberrant peritoneal environment of cytokines might be very closely linked to the pathogenesis and pathophysiology of endometriosis. We investigated the functional roles of IL-9 on endometriosis. The proportion of CD4+IL-9+ T cells in the peritoneal fluid of patients with endometriosis was significantly higher than that of patients without endometriosis. The expression level of IL-9 receptor in ovarian endometrioma was significantly greater than that in endometrium of the uterus. Furthermore, in cultured stromal cells derived from ovarian endometrioma, IL-9 markedly elevated the expression of IL-8 and COX-2, and IL-9 additively stimulated IL-8 expression in the presence of TNF-α. This study revealed that IL-9 produced by helper T cells contributes to the inflammation in endometriosis. We provided therapeutic potential of IL-9 and IL-9-producing T cells in endometriosis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果により、子宮内膜症におけるIL-9産生ヘルパーT細胞の割合の変化が明らかとなり、IL-9がIL-8を介する子宮内膜症の炎症、進展において重要な働きを持つことが示唆された。IL-9は子宮内膜症の新たな治療対象となる可能性がある。しかし、in vitroの研究による限界も存在するため、今後in vivoでの検討およびIL-9の免疫応答に対する役割について検討が必要である。
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis2022
Author(s)
Tarumi Y, Mori T, Shimura K, Izumi Y, Okimura H, Kataoka H, Kokabu T, Ito F, Koshiba A, Khan KN, Kusuki I, Kitawaki J.
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Journal Title
J Clin Endocrinol Metab.
Volume: 107
Issue: 6
Pages: 1552-1559
DOI
Related Report
Peer Reviewed
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[Presentation] Interleukin-9 produced by helper T cells induces inflammatory responses in endometriosis2021
Author(s)
Yosuke Tarumi, Taisuke Mori, Fumitake Ito, Akemi Koshiba, Hisashi Kataoka, Eiko Maeda, Hiroyuki Okimura, Takuya Sugahara, Koki Shimura, Kanae Ogawa, Maya Fujii, Izumi Kusuki, Khaleque Khan, Jo Kitawaki
Organizer
14th World Congress on Endometriosis
Related Report
Int'l Joint Research
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