Asthma is a heterogeneous disease, and abnormal activation of T cells is the driving link of asthma’s pathophysiological changes. Dual-positive Th2–Th17 cells, as newly discovered T-helper cells, have the functions of Th2 and Th17 cells and can coproduce Th2 and Th17 cytokines. Previous studies have shown that dual-positive Th2–Th17 cells increase the chances of asthma and correlate with asthma severity. However, the exact role of dual-positive Th2–Th17 cells in asthma is not known. Since there is no mature differentiation method for dual-positive Th2–Th17 cells, the present study aimed to clarify the strict differentiation conditions and reveal how dual-positive Th2–Th17 cells regulate asthma phenotypes. In this study, we confirmed that IL-1β, IL-6, anti-IFN-γ, and IL-21 promoted biphenotypic cell differentiation. Moreover, more proportion of dual-positive Th2–Th17 cells can be obtained by conditioned differentiation of mouse CD4⁺ T cells after classical allergic asthma modeling. Before asthma modeling, adoptive dual-positive Th2–Th17 cells promoted T cells to differentiate into the same biphenotype cells and exacerbated the severity of asthma. Together, our results clarify the differentiation conditions of dual-positive Th2–Th17 cells and further confirm that it stimulates asthma T cells to differentiate into the same biphenotype cells, leading to exacerbation of asthma.

中文翻译：

---

双阳性 Th2-Th17 细胞比例增加促进了更严重的哮喘亚型

哮喘是一种异质性疾病，T细胞异常激活是哮喘病理生理变化的驱动环节。双阳性Th2-Th17细胞作为新发现的T辅助细胞，具有Th2和Th17细胞的功能，可以共同产生Th2和Th17细胞因子。先前的研究表明，双阳性 Th2-Th17 细胞会增加患哮喘的几率并与哮喘严重程度相关。然而，双阳性 Th2-Th17 细胞在哮喘中的确切作用尚不清楚。由于Th2-Th17双阳性细胞尚无成熟的分化方法，本研究旨在阐明严格的分化条件，揭示Th2-Th17双阳性细胞如何调节哮喘表型。在本研究中，我们证实 IL-1 β、IL-6、抗 IFN- γ和 IL-21 促进双表型细胞分化。此外，在经典过敏性哮喘模型后，通过条件分化小鼠 CD4 ⁺ T 细胞可以获得更多比例的双阳性 Th2-Th17 细胞。在哮喘建模之前，过继性双阳性 Th2-Th17 细胞促进 T 细胞分化为相同的双表型细胞，加剧了哮喘的严重程度。总之，我们的结果阐明了双阳性 Th2-Th17 细胞的分化条件，并进一步证实它刺激哮喘 T 细胞分化为相同的双表型细胞，导致哮喘恶化。