Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified interleukin (IL)-9-producing type 2 innate lymphoid cells (ILC2s) as the mediators of a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation and activation of regulatory T (T_reg) cells, and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent T_reg activation and effectively induced resolution of inflammation and protection of bone. Patients with rheumatoid arthritis in remission exhibited high numbers of IL-9⁺ ILC2s in joints and the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses.

中文翻译：

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产生白介素9的2型先天淋巴样细胞对炎症的缓解

诸如关节炎之类的炎症性疾病是无法自发解决的慢性疾病。尽管触发关节炎的细胞因子和细胞途径已得到明确定义，但导致炎症消退的细胞因子和细胞途径尚未完全鉴定。在这里，我们确定了产生白介素（IL）-9的2型先天淋巴样细胞（ILC2s）作为协调慢性炎症消退的分子和细胞途径的介质。在小鼠中，IL-9的缺失会削弱ILC2的增殖和调节性T（T _reg）细胞的活化，并导致慢性关节炎，并伴有过度的软骨破坏和骨质流失。相反，用IL-9治疗可促进ILC2依赖性T _reg激活并有效诱导炎症消退和保护骨骼。缓解的类风湿关节炎患者在关节和循环中表现出大量的IL-9 ⁺ ILC2s。因此，促进IL-9介导的ILC2活化可以提供诱导炎症消退而不是抑制炎症反应的新型治疗方法。