Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany; Department of Orthopaedic Surgery, The University of Tokyo, Tokyo, Japan; Deutsches Zentrum für Immuntherapie (DZI), Germany.
Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany; Deutsches Zentrum für Immuntherapie (DZI), Germany.
Bone. 2020 Jul;136:115335. doi: 10.1016/j.bone.2020.115335. Epub 2020 Mar 30.
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.
虽然 T 细胞在骨骼稳态调节中的作用已得到明确界定，但人们对先天淋巴细胞（ILC）在骨骼中的作用知之甚少。ILC 是先天免疫细胞，其细胞因子表达模式与 T 细胞相似，但缺乏 T 细胞受体。在这项研究中，我们使用缺失和功能获得模型表明，2 型先天淋巴细胞（ILC2）在体外强烈抑制破骨细胞的生成，并且在体内稳态条件下有利于骨骼稳态。此外，通过体内显著下调破骨细胞数量，ILC2 的过继转移完全消除了卵巢切除术诱导的骨丢失。ILC2 在体外和体内对破骨细胞的抑制作用以及对卵巢切除术诱导的骨丢失的保护作用与其表达的 IL-4 和 IL-13 以及骨髓靶细胞上的 STAT6 激活有关，因为 ILC2 中 IL-4/IL-13 的缺失或破骨细胞前体中的 STAT6 缺失消除了 ILC2 的抗破骨生成作用。综上所述，这些发现表明 ILC2 可被视为骨骼稳态的有效调节者。
