2023 Fiscal Year Final Research Report
Role of gp130-dependent cytokine signaling in pulmonary hypertension
| Project/Area Number |
21K08070
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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 53020:Cardiology-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Ishibashi Tomohiko 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (30722285)
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| Co-Investigator(Kenkyū-buntansha) |
稲垣 薫克 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (20638366)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | 肺高血圧症 / interleukin-6 / CD4陽性細胞 / 肺血管リモデリング |
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| Outline of Final Research Achievements |
Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of the IL-6 receptor, we revealed that a CD4+ T cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. These findings suggest that IL-6/gp130 signaling in CD4+ T cells plays a critical role in the pathogenesis of PAH.
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| Free Research Field |
循環器内科学、血管生物学、血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
肺高血圧症は、治療薬の開発が進み治療法が進歩しつつある疾患であるが、薬剤反応性が低い患者においては未だに予後不良の疾患である。本研究では免疫細胞のCD4陽性T細胞における炎症性サイトカインのIL-6シグナルが肺高血圧症の病態形成に重要な役割を果たしていることを明らかにした。本研究から、免疫細胞における炎症シグナルを抑制することで、炎症に着目した新たな治療法の確立といった肺高血圧症における創薬の可能性が期待できる。
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