吸血蚊のアミノ酸代謝ダイナミクスを解明~蚊の栄養マネジメントが新しい防除技術の鍵に~

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2025-11-27 理化学研究所

理化学研究所らの研究チームは、固形がんに対する難題とされてきた免疫細胞療法(CAR-T細胞療法)の弱点を克服する新戦略を報告した。通常、CAR-T細胞は血液がんには有効だが、固形がんでは腫瘍内部へ浸潤できず効果が限定的であった。今回、研究グループは 腫瘍微小環境へ浸透しやすい特性を持つ受容体や接着分子を導入した「改良CAR-T細胞」 を設計。これにより、マウス固形がんモデルにおいて、CAR-T細胞の腫瘍内への浸潤性と抗腫瘍効果が大幅に向上した。さらに、T細胞の疲弊(機能低下)を抑えつつ、持続的な抗がん作用を維持することにも成功。これにより、これまで“CAR-T が効きにくい”とされてきた固形がんにも、有効な免疫療法の道が開かれた。今回の成果は、がん治療におけるCAR-T細胞療法の適用範囲拡大に向けた重要なブレークスルーと期待される。

吸血蚊のアミノ酸代謝ダイナミクスを解明~蚊の栄養マネジメントが新しい防除技術の鍵に~
吸血蚊の体内に含まれるアミノ酸の時間的変化を解析・可視化

<関連情報>

アミノ酸プロファイルの時間的変化が蚊の生理とネッタイシマカの卵の成熟を調整する Temporal changes in amino acid profiles coordinate mosquito physiology and egg maturation in Aedes aegypti

Yusuke Kato,Ayano Oi,Naoshi Dohmae,Fumiaki Obata & Chisako Sakuma
BMC Biology  Published:27 November 2025
DOI:https://doi.org/10.1186/s12915-025-02460-z

Abstract

Background

Female Aedes aegypti mosquitoes utilize host blood to support egg maturation by digesting, absorbing, and metabolizing its components. Among these, amino acids are essential as both signaling molecules and building blocks for yolk proteins. While their overall importance is established, the individual dynamics and regulation of each amino acid remain insufficiently understood.

Results

We systematically profiled free and protein-bound amino acids in whole bodies, ovaries, and excreta over time after blood feeding, revealing distinct temporal dynamics across amino acids. Notably, tyrosine, enriched in yolk proteins, exhibited a biphasic pattern: a transient decrease between 6 and 9 h post blood meal, followed by accumulation during egg maturation. We also performed RNA-seq and found that amino acid metabolism is partially regulated by 20-hydroxyecdysone (20E), indicating hormonal control of amino acid homeostasis. Integrating RNA-seq analysis with amino acid profiling further suggested an adaptation to metabolic imbalance between host blood and ovaries. The early decrease in tyrosine was attributed to enzymatic degradation by 4-hydroxyphenylpyruvate dioxygenase (Hpd), whose expression is induced by 20E, a key hormone orchestrating post-blood-feeding gene expression and egg maturation. Pharmacological inhibition of Hpd caused tyrosine accumulation and increased lethality, indicating that tight regulation of tyrosine catabolism is essential for survival.

Conclusions

This study highlights the temporally coordinated metabolism of individual amino acids during mosquito reproduction. Our dataset serves as a valuable resource for understanding nutrient allocation with endocrine regulation, as well as a foundation for developing novel strategies to disrupt mosquito survival by targeting the metabolic enzymes.

医療・健康
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