细胞因子
免疫学
白细胞介素9
胸腺基质淋巴细胞生成素
启动(农业)
白细胞介素13
转录因子
表型
先天性淋巴细胞
生物
人口
过敏性炎症
炎症
白细胞介素
医学
免疫系统
获得性免疫系统
遗传学
基因
植物
发芽
环境卫生
作者
Michelle Chu,Abigail Pajulas,Cameron R. Rostron,Cherry C.L. Cheung,Maya S. Krishnan,Jilu Zhang,Anthony J. Cannon,Mark H. Kaplan
标识
DOI:10.1016/j.mucimm.2024.03.006
摘要
Multi-cytokine-producing Th9 cells secrete IL-9 and type 2 cytokines and mediate mouse and human allergic inflammation. However, the cytokines that promote a multi-cytokine secreting phenotype have not been defined. Tumor necrosis factor superfamily member TL1A signals through its receptor DR3 to increase IL-9. Here we demonstrate that TL1A increases expression of IL-9 and IL-13 co-expressing cells in murine Th9 cell cultures, inducing a multi-cytokine phenotype. Mechanistically, this is linked to histone modifications allowing for increased accessibility at the Il9 and Il13 loci. We further show that TL1A alters the transcription factor network underlying expression of IL-9 and IL-13 in Th9 cells and increases binding of transcription factors to Il9 and Il13 loci. TL1A-priming enhances the pathogenicity of Th9 cells in murine models of allergic airway disease through the increased expression of IL-9 and IL-13. Lastly, in both chronic and memory-recall models of allergic airway disease, blockade of TL1A signaling decreases the multi-cytokine Th9 cell population and attenuates the allergic phenotype. Taken together, these data demonstrate that TL1A promotes the development of multi-cytokine Th9 cells that drive allergic airway diseases and that targeting pathogenic T helper cell-promoting cytokines could be an effective approach for modifying disease.
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