Group 2 innate lymphoid cells in bone marrow regulate osteoclastogenesis in a reciprocal manner via RANKL, GM-CSF and IL-13
Group 2 innate lymphoid cells in bone marrow regulate osteoclastogenesis in a reciprocal manner via RANKL, GM-CSF and IL-13
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DOI：
10.1093/intimm/dxab062
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发表时间：
2021-09-09
影响因子：
4.4
通讯作者：
Moro, Kazuyo
中科院分区：
文献类型：
--
作者：
Momiuchi, Yoshiki;Motomura, Yasutaka;Moro, Kazuyo
2组先天淋巴样细胞（Group 2 innate lymphoid cells, ILC2s）是一种组织驻留细胞，通过感知周围环境因子在不同器官中发挥不同作用。最初，人们认为骨髓中的ILC2s是全身ILC2s的祖细胞，其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ILC2s本身可能作为一种独特的效应物在BM中发挥特定的作用。在这里，我们证明BM ILC2s高度表达核因子κ B配体受体激活因子（RANKL），这是一种强大的破骨细胞分化和激活的细胞因子，ILC2s上RANKL的表达被白细胞介素(IL)-2、IL-7和全反式维甲酸（ATRA）上调。在IL-7存在的情况下，BM ILC2s与BM来源的单核细胞/巨噬细胞谱系细胞（BMMs）共培养，诱导酒石酸抗性酸性磷酸酶（TRAP）阳性破骨细胞以rankl依赖的方式分化。相比之下，IL-33刺激BM ILC2s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的产生将BMMs分化为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，在IL-7 + atra诱导的骨质流失小鼠模型中，ILC2s的缺失显著损害了体内破骨细胞的活性。这些结果表明，ILC2s调节破骨细胞的激活，并在稳态和il -33诱导的炎症中促进骨稳态。
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 kappa B 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.