小鼠Th2细胞外泌体通过表面细胞因子IL-3促进嗜酸性粒细胞存活
2025/08/01
摘要
背景：细胞外泌体（EVs）在免疫反应期间介导细胞间通信。EVs在呼吸道生物液体中含量丰富，且在炎症期间肺部EVs的组成会发生变化。
目的：我们旨在量化T细胞对嗜酸性粒细胞性肺部炎症中气道EVs的贡献，并确定其在2型炎症反应中的功能。
方法：通过遗传性膜标记与单囊泡流式细胞术相结合，量化用卵清蛋白或屋尘螨挑战的小鼠气道中的T细胞EVs。从小鼠Th2细胞培养中纯化EVs，并通过流式细胞术和RNA测序评估其对嗜酸性粒细胞的功能。将Th2细胞EVs注入小鼠肺部，以确定其对肺部嗜酸性粒细胞增多症的影响。最后，使用抑制剂和阻断抗体测试EV蛋白货物的功能。
结果：在卵清蛋白或屋尘螨诱导的炎症后，小鼠气道中的T细胞EVs增加。Th2细胞分泌的EVs在体外抑制嗜酸性粒细胞的凋亡，并诱导激活途径。这种效应依赖于通过T细胞受体的再刺激。在急性嗜酸性粒细胞炎症期间，Th2细胞EVs在体内延长了嗜酸性粒细胞增多症。Th2细胞EVs携带细胞因子IL-3作为表面生物分子，通过激活嗜酸性粒细胞中依赖Jak1/2的促存活程序来抑制凋亡。
结论：Th2细胞EVs通过EV表面生物分子IL-3促进嗜酸性粒细胞存活，支持EVs作为基于细胞因子通信的载体在肺部炎症中的作用。
Mouse Th2 cell extracellular vesicles promote eosinophil survival through the surface cytokine cargo IL-3
Kaitlyn E Bunn, Brenna G Giese-Byrne, Alexander M Blatt, Dawn C Newcomb, Heather H Pua
Abstract
Background: Extracellular vesicles (EVs) mediate intercellular communication during immune responses. EVs are abundant in respiratory biofluids, and the composition of EVs in the lung changes during inflammation.
Objective: We aimed to quantify the contribution of T cells to airway EVs in eosinophilic lung inflammation and ascertain their function during a type 2 inflammatory response.
Methods: Genetic membrane tagging was combined with single vesicle flow cytometry to quantify T cell EVs in the airways of mice challenged with ovalbumin or house dust mite. EVs were purified from mouse T helper type 2 (Th2) cell cultures and their functions on eosinophils assessed by flow cytometry and RNA sequencing. Th2 cell EVs were instilled into the lungs of mice to determine effects on lung eosinophilia. Finally, the function of an EV protein cargo was tested using inhibitors and blocking antibodies.
Results: T cell EVs are increased in the airways of mice after ovalbumin or house dust mite induced inflammation. EVs secreted by Th2 cells inhibit apoptosis and induce activating pathways in eosinophils in vitro. This effect depends on re-stimulation through the T cell receptor. Th2 cell EVs prolong eosinophilia in vivo during acute eosinophilic inflammation. Th2 cell EVs carry the cytokine IL-3 as a surface cargo, which inhibits apoptosis by activating Jak1/2-dependent pro-survival programs in eosinophils.
Conclusion: Th2 cell EVs promote eosinophil survival through the EV cargo IL-3, supporting a role for EVs as vehicles of cytokine-based communication in lung inflammation.
背景：细胞外泌体（EVs）在免疫反应期间介导细胞间通信。EVs在呼吸道生物液体中含量丰富，且在炎症期间肺部EVs的组成会发生变化。
目的：我们旨在量化T细胞对嗜酸性粒细胞性肺部炎症中气道EVs的贡献，并确定其在2型炎症反应中的功能。
方法：通过遗传性膜标记与单囊泡流式细胞术相结合，量化用卵清蛋白或屋尘螨挑战的小鼠气道中的T细胞EVs。从小鼠Th2细胞培养中纯化EVs，并通过流式细胞术和RNA测序评估其对嗜酸性粒细胞的功能。将Th2细胞EVs注入小鼠肺部，以确定其对肺部嗜酸性粒细胞增多症的影响。最后，使用抑制剂和阻断抗体测试EV蛋白货物的功能。
结果：在卵清蛋白或屋尘螨诱导的炎症后，小鼠气道中的T细胞EVs增加。Th2细胞分泌的EVs在体外抑制嗜酸性粒细胞的凋亡，并诱导激活途径。这种效应依赖于通过T细胞受体的再刺激。在急性嗜酸性粒细胞炎症期间，Th2细胞EVs在体内延长了嗜酸性粒细胞增多症。Th2细胞EVs携带细胞因子IL-3作为表面生物分子，通过激活嗜酸性粒细胞中依赖Jak1/2的促存活程序来抑制凋亡。
结论：Th2细胞EVs通过EV表面生物分子IL-3促进嗜酸性粒细胞存活，支持EVs作为基于细胞因子通信的载体在肺部炎症中的作用。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
（J Allergy Clin Immunol. 2025 Jun 10:S0091-6749(25)00622-0. doi: 10.1016/j.jaci.2025.05.027.）
Mouse Th2 cell extracellular vesicles promote eosinophil survival through the surface cytokine cargo IL-3
Kaitlyn E Bunn, Brenna G Giese-Byrne, Alexander M Blatt, Dawn C Newcomb, Heather H Pua
Abstract
Background: Extracellular vesicles (EVs) mediate intercellular communication during immune responses. EVs are abundant in respiratory biofluids, and the composition of EVs in the lung changes during inflammation.
Objective: We aimed to quantify the contribution of T cells to airway EVs in eosinophilic lung inflammation and ascertain their function during a type 2 inflammatory response.
Methods: Genetic membrane tagging was combined with single vesicle flow cytometry to quantify T cell EVs in the airways of mice challenged with ovalbumin or house dust mite. EVs were purified from mouse T helper type 2 (Th2) cell cultures and their functions on eosinophils assessed by flow cytometry and RNA sequencing. Th2 cell EVs were instilled into the lungs of mice to determine effects on lung eosinophilia. Finally, the function of an EV protein cargo was tested using inhibitors and blocking antibodies.
Results: T cell EVs are increased in the airways of mice after ovalbumin or house dust mite induced inflammation. EVs secreted by Th2 cells inhibit apoptosis and induce activating pathways in eosinophils in vitro. This effect depends on re-stimulation through the T cell receptor. Th2 cell EVs prolong eosinophilia in vivo during acute eosinophilic inflammation. Th2 cell EVs carry the cytokine IL-3 as a surface cargo, which inhibits apoptosis by activating Jak1/2-dependent pro-survival programs in eosinophils.
Conclusion: Th2 cell EVs promote eosinophil survival through the EV cargo IL-3, supporting a role for EVs as vehicles of cytokine-based communication in lung inflammation.
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