IL-33/TGF-β/IL-4诱导的骨髓源性DC9亚群促进Th9分化和过敏性气道炎症
IL-33/TGF-β/IL-4-induced bone marrow-derived DC9 subset promotes Th9 differentiation and allergic airway inflammation.
摘要(中文译文)
树突状细胞（DCs）是专业的抗原提呈细胞，在发育和功能上表现出显著异质性。本研究发现，在筛选的17种细胞因子中，仅IL-33能够在体外诱导DCs呈现Th9型细胞因子谱，包括IL-9、IL-4和IL-13。DCs对IL-33的应答可被TGF-β和IL-4协同增强，从而定义了一个被称为DC9的独特亚群。转录组分析显示，与常规DCs相比，DC9具有独特的基因表达特征，尤其在细胞因子/趋化因子基因簇方面。在机制上，DC9极化依赖于JAK-STAT6-IRF4信号通路。在功能上，DC9在体外优先驱动初始CD4 T细胞向Th9细胞分化。在卵清蛋白诱导的过敏性气道炎症小鼠模型中，肺部可检测到DC9细胞，过继转移DC9可加重疾病严重程度，并增加肺部Th9细胞。综上所述，我们鉴定出DC9是一种由IL-33/TGF-β/IL-4通过JAK-STAT6-IRF4轴诱导的新型DC亚群，其促进Th9分化并加重过敏性气道炎症。
Abstract
Dendritic cells (DCs) are professional antigen-presenting cells that exhibit significant heterogeneity in development and function. This study found that among 17 cytokines screened, only IL-33 could induce DCs to display a Th9-type cytokine profile, including IL-9, IL-4, and IL-13, in vitro. The response of DCs to IL-33 was synergistically enhanced by TGF-β and IL-4, defining a distinct subset termed DC9. Transcriptomic analysis revealed that DC9 possesses a unique gene expression signature, particularly in cytokine/chemokine clusters, compared to conventional DCs. Mechanistically, DC9 polarization depends on the JAK-STAT6-IRF4 signaling pathway. Functionally, DC9 preferentially drives naive CD4 T cell differentiation toward Th9 cells in vitro. In an ovalbumin-induced allergic airway inflammatory mouse model, DC9 cells were detectable in lungs and adoptive transfer of DC9 exacerbated disease severity, and increased pulmonary Th9 cells. Collectively, we identify DC9 as a novel DC subset induced by IL-33/TGF-β/IL-4 through the JAK-STAT6-IRF4 axis, which promotes Th9 differentiation and aggravates allergic airway inflammation.
如何引用
AMA
Yifang Chen, Qian Zhang, Na Li, Zhaoqi Zhang, Tong Lei, Han Guo, et al. IL-33/TGF-β/IL-4-induced bone marrow-derived DC9 subset promotes Th9 differentiation and allergic airway inflammation.. Cell reports. 2026; doi:10.1016/j.celrep.2026.117519.
APA
Yifang Chen, Qian Zhang, Na Li, Zhaoqi Zhang, Tong Lei, Han Guo, et al (2026). IL-33/TGF-β/IL-4-induced bone marrow-derived DC9 subset promotes Th9 differentiation and allergic airway inflammation.. Cell reports. https://doi.org/10.1016/j.celrep.2026.117519
GB/T 7714
Yifang Chen, Qian Zhang, Na Li, Zhaoqi Zhang, Tong Lei, Han Guo, et al. IL-33/TGF-β/IL-4-induced bone marrow-derived DC9 subset promotes Th9 differentiation and allergic airway inflammation.[J]. Cell reports, 2026 doi:10.1016/j.celrep.2026.117519.
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