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2023 Fiscal Year Final Research Report

Immune disfunction in lymphedema: Peripheral T cell investigation compared with healthy controls

Research Project

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Project/Area Number 21K09768
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56070:Plastic and reconstructive surgery-related
Research InstitutionJapanese Foundation for Cancer Research (2023)
Hiroshima University (2021-2022)

Principal Investigator

IMAI Hirofumi  公益財団法人がん研究会, 有明病院 形成外科, 副医長 (10868847)

Co-Investigator(Kenkyū-buntansha) 川瀬 孝和  藤田医科大学, 国際再生医療センター, 准教授 (30463194)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywordsリンパ浮腫 / T細胞 / T細胞受容体 / リンパ管静脈吻合術 / マイクロサージャリー
Outline of Final Research Achievements

Complications of lymphedema include cellulitis and angiosarcoma, suggesting the presence of immunodeficiency. Lymphaticovenous anastomosis (LVA) has been reported to alleviate these, but its mechanism remains unclear. In this study, we targeted 21 cases of lymphedema and 20 healthy individuals, performing LVA on the lymphedema group and conducting blood sampling one year post-surgery. We calculated the exhaustion factor (PD-1) on T cells and the diversity index of T cell receptors (TCR). The expression levels (%) of PD-1 on CD4+ T cells in the lymphedema group, post-LVA group, and healthy group were 30.7, 27.1, and 19.9, respectively. The diversity indices of TCR were 44.1, 200.5, and 151.0, respectively. In the lymphedema group, compared to the healthy group, PD-1 expression on T cells was higher and TCR diversity was lower. Conversely, after LVA, the expression of exhaustion factors decreased, and TCR diversity recovered, suggesting an improvement in immune function.

Free Research Field

リンパ浮腫

Academic Significance and Societal Importance of the Research Achievements

本研究はヒトリンパ浮腫を対象とした免疫系に関する初めての研究である。リンパ浮腫におけるT細胞の疲弊化とクローンの多様性低下を指摘し、長らく不明だった免疫不全状態の原因の一端を解明した。また、Th1、Th17細胞の増加がリンパ浮腫の進展に関与している可能性を指摘し、従来のTh2のみでない様々な炎症性T細胞に注目する必要があることを提議した。更にLVAがリンパ浮腫のT細胞に与える影響に関しても初めて報告し、LVAの浮腫改善効果のみではない免疫上の有用性を示した。リンパ浮腫における免疫不全の要因とLVAがもたらす新たな有用性を基礎医学の観点からエビデンスを構築する非常に画期的な研究であると言える。

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Published: 2025-01-30  

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