Objectives: Exosomes are extracellular vesicles released from various inflammatory cells, such as T cells, B cells, dendritic cells (DCs), and mast cells, which have been implicated in the modulation of immune response in asthma. This study aimed to investigate whether exosomes from DCs activated by thymic stromal lymphopoietin (TSLP) play a role in T-helper cell differentiation through the OX40 ligand (OX40L). Methods: Serum samples from patients with asthma were collected to measure the levels of OX40L, T-helper type 1 (Th1) cytokine interferon (IFN)-γ, and T-helper type 2 (Th2) cytokine interleukin (IL)-4 by enzyme-linked immunosorbent assay (ELISA). Exosomes were isolated from TSLP-activated DCs and co-cultured with CD4+ T cells. Western blot and ELISA assays were used to measure the levels of OX40L, IFN-γ, and IL-4 in DCs and CD4+ T cells. Flow cytometry was applied to detect Th1 and Th2 cells. Results: OX40L and IL-4 were increased and IFN-γ was decreased in serum from asthmatic patients compared with healthy controls. TSLP induced DCs to express OX40L in released exosomes, which could promote proliferation of CD4+ T cells, elevate the level of IL-4, and promote Th2 differentiation. Conclusion: Blockade of OX40L in DC-derived exosomes could inhibit exosome-mediated CD4+ T proliferation and Th2 differentiation.

中文翻译：

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来自胸腺基质淋巴细胞生成素激活的树突细胞的外泌体通过 OX40 配体促进 Th2 分化

目的：外泌体是从各种炎症细胞（如 T 细胞、B 细胞、树突状细胞 (DC) 和肥大细胞）释放的细胞外囊泡，这些细胞与调节哮喘免疫反应有关。本研究旨在研究来自胸腺基质淋巴细胞生成素 (TSLP) 激活的 DCs 的外泌体是否通过 OX40 配体 (OX40L) 在 T 辅助细胞分化中发挥作用。方法：收集哮喘患者的血清样本，通过测定OX40L、T-helper 1型（Th1）细胞因子干扰素（IFN）-γ和T-helper 2型（Th2）细胞因子白细胞介素（IL）-4的水平。酶联免疫吸附试验 (ELISA)。从 TSLP 激活的 DC 中分离外泌体，并与 CD4+ T 细胞共培养。蛋白质印迹和 ELISA 测定用于测量 DC 和 CD4+ T 细胞中 OX40L、IFN-γ 和 IL-4 的水平。流式细胞术检测Th1和Th2细胞。结果：与健康对照相比，哮喘患者血清中OX40L和IL-4升高，IFN-γ降低。TSLP 诱导 DCs 在释放的外泌体中表达 OX40L，可促进 CD4+T 细胞增殖，提高 IL-4 水平，促进 Th2 分化。结论：阻断 DC 衍生的外泌体中的 OX40L 可以抑制外泌体介导的 CD4+T 增殖和 Th2 分化。