Department of Experimental Medicine, University of Perugia, 06132 Perugia, Italy.
Department of Medical and Biological Science, University of Udine, 33100 Udine, Italy.
Nat Commun. 2017 Jan 16;8:14017. doi: 10.1038/ncomms14017.
T helper 9 (Th9) cells contribute to lung inflammation and allergy as sources of interleukin-9 (IL-9). However, the mechanisms by which IL-9/Th9 mediate immunopathology in the lung are unknown. Here we report an IL-9-driven positive feedback loop that reinforces allergic inflammation. We show that IL-9 increases IL-2 production by mast cells, which leads to expansion of CD25 type 2 innate lymphoid cells (ILC2) and subsequent activation of Th9 cells. Blocking IL-9 or inhibiting CD117 (c-Kit) signalling counteracts the pathogenic effect of the described IL-9-mast cell-IL-2 signalling axis. Overproduction of IL-9 is observed in expectorates from cystic fibrosis (CF) patients, and a sex-specific variant of IL-9 is predictive of allergic reactions in female patients. Our results suggest that blocking IL-9 may be a therapeutic strategy to ameliorate inflammation associated with microbial colonization in the lung, and offers a plausible explanation for gender differences in clinical outcomes of patients with CF.
辅助性 T 细胞 9（Th9）细胞作为白细胞介素 9（IL-9）的来源，有助于肺部炎症和过敏反应。然而，IL-9/Th9 介导肺部免疫病理学的机制尚不清楚。在这里，我们报告了一个由 IL-9 驱动的正反馈回路，该回路增强了过敏炎症。我们表明，IL-9 增加了肥大细胞中 IL-2 的产生，这导致了 CD25 型 2 先天淋巴细胞（ILC2）的扩增，并随后激活了 Th9 细胞。阻断 IL-9 或抑制 CD117（c-Kit）信号可对抗所描述的 IL-9-肥大细胞-IL-2 信号轴的致病作用。囊性纤维化（CF）患者的痰液中观察到 IL-9 的过度产生，并且 IL-9 的性别特异性变体可预测女性患者的过敏反应。我们的研究结果表明，阻断 IL-9 可能是一种改善与肺部微生物定植相关的炎症的治疗策略，并为 CF 患者的临床结局存在性别差异提供了合理的解释。
