Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells that play different roles in different organs by sensing surrounding environmental factors. Initially, it was thought that ILC2s in bone marrow (BM) are progenitors for systemic ILC2s, which migrate to other organs and acquire effector functions. However, accumulating evidence that ILC2s differentiate in peripheral tissues suggests that BM ILC2s may play a specific role in the BM as a unique effector per se. Here, we demonstrate that BM ILC2s highly express the receptor activator of nuclear factor κB ligand (RANKL), a robust cytokine for osteoclast differentiation and activation, and RANKL expression on ILC2s is up-regulated by interleukin (IL)-2, IL-7 and all-trans retinoic acid (ATRA). BM ILC2s co-cultured with BM-derived monocyte/macrophage lineage cells (BMMs) in the presence of IL-7 induce the differentiation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in a RANKL-dependent manner. In contrast, BM ILC2s stimulated with IL-33 down-regulate RANKL expression and convert BMMs differentiation into M2 macrophage-like cells rather than osteoclasts by granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-13 production. Intravital imaging using two-photon microscopy revealed that a depletion of ILC2s prominently impaired in vivo osteoclast activity in an IL-7 plus ATRA-induced bone loss mouse model. These results suggest that ILC2s regulate osteoclast activation and contribute to bone homeostasis in both steady state and IL-33-induced inflammation.

中文翻译：

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骨髓中的第 2 组先天淋巴细胞通过 RANKL、GM-CSF 和 IL-13 以交互方式调节破骨细胞生成

第 2 组先天淋巴细胞 (ILC2) 是组织驻留细胞，通过感知周围环境因素在不同器官中发挥不同作用。最初，人们认为骨髓 (BM) 中的 ILC2 是全身性 ILC2 的祖细胞，它们迁移到其他器官并获得效应功能。然而，越来越多的证据表明 ILC2s 在外周组织中分化表明 BM ILC2s 可能在 BM 中发挥特定作用，作为一种独特的效应器。. 在这里，我们证明 BM ILC2s 高度表达核因子 κB 配体 (RANKL) 的受体激活剂，RANKL 是破骨细胞分化和激活的强大细胞因子，ILC2s 上的 RANKL 表达被白细胞介素 (IL)-2、IL-7 上调和全反式维甲酸 (ATRA)。在 IL-7 存在下与 BM 衍生的单核细胞/巨噬细胞谱系细胞 (BMM) 共培养的 BM ILC2s 以 RANKL 依赖性方式诱导抗酒石酸酸性磷酸酶 (TRAP) 阳性破骨细胞的分化。相比之下，用 IL-33 刺激的 BM ILC2 下调 RANKL 表达，并通过粒细胞巨噬细胞集落刺激因子 (GM-CSF) 和 IL-13 产生将 BMM 分化转化为 M2 巨噬细胞样细胞而不是破骨细胞。使用双光子显微镜的活体成像显示 ILC2 的消耗显着受损IL-7 加 ATRA 诱导的骨丢失小鼠模型中的体内破骨细胞活性。这些结果表明，ILC2s 调节破骨细胞活化，并在稳态和 IL-33 诱导的炎症中促进骨稳态。