Type 2 innate lymphoid cells inhibit the differentiation of osteoclasts and protect from ovariectomy-induced bone loss
Type 2 innate lymphoid cells inhibit the differentiation of osteoclasts and protect from ovariectomy-induced bone loss
复制标题
DOI：
10.1016/j.bone.2020.115335
复制
发表时间：
2020-07-01
期刊：
影响因子：
4.1
通讯作者：
Zaiss, Mario M.
中科院分区：
文献类型：
--
作者：
Omata, Yasunori;Frech, Michael;Zaiss, Mario M.
虽然 T 细胞在骨稳态调节中的作用已明确，但对于先天淋巴细胞 (ILC) 对骨的作用知之甚少。 ILC 是先天免疫细胞，与 T 细胞共享细胞因子表达模式，但缺乏 T 细胞受体。在这项研究中，我们使用功能丧失和获得模型证明，2 型 ILC (ILC2) 在体外有效抑制骨吸收破骨细胞的生成，并在体内稳态条件下有利地影响骨稳态。此外，ILC2的过继转移通过显着下调体内破骨细胞数量，完全消除了卵巢切除术引起的骨质流失。 ILC2在体外和体内对破骨细胞的抑制作用以及对卵巢切除引起的骨丢失的保护作用与其IL-4和IL-13的表达以及骨髓靶细胞上STAT6的激活有关，因为ILC2中IL-4/IL-13或破骨细胞前体中STAT6的缺失消除了ILC2的抗破骨细胞生成作用。总而言之，这些发现表明 ILC2 必须被视为骨稳态的有效调节剂。
While the role of T cells in the regulation of bone homeostasis is well defined, little is known about the role of innate lymphoid cells (ILCs) on bone. ILCs are innate immune cells that share cytokine expression patterns with T cells but lack the T cell receptor. In this study we show that type 2 ILCs (ILC2) potently inhibit the generation of bone resorbing osteoclasts in vitro as well as favorably influence bone homeostasis under steady state conditions in vivo using loss and gain of function models. Furthermore, adoptive transfer of ILC2 completely abrogated ovariectomy-induced bone loss by significantly down-regulating osteoclast numbers in vivo. The suppressive effects of ILC2s on osteoclasts in vitro and in vivo as well as the protection from ovariectomy-induced bone loss were linked to their expression of IL-4 and IL-13 as well as STAT6 activation on the myeloid target cell, since deletion of IL-4/IL-13 in ILC2s or STAT6 in osteoclast precursors abrogated the anti-osteoclastogenic effect of ILC2s. Taken together, these findings show that ILC2 have to be considered as potent regulators of bone homeostasis.