DCIR Maintains Bone Homeostasis by Regulating IFN-γ Production in T Cells
DCIR Maintains Bone Homeostasis by Regulating IFN-γ Production in T Cells
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DOI：
10.4049/jimmunol.1500273
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发表时间：
2015-06-15
影响因子：
4.4
通讯作者：
Iwakura, Yoichiro
中科院分区：
文献类型：
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作者：
Maruhashi, Takumi;Kaifu, Tomonori;Iwakura, Yoichiro
树突状细胞免疫受体(DCIR)是一种主要表达于DC的C型凝集素受体。DCIR(-/-)小鼠自发发生自身免疫性吻合口炎和强直，并伴有纤维软骨增殖和异位骨化。然而，Dcir(-/-)小鼠新生骨/软骨形成的机制尚不清楚。在这项研究中，我们证明了DCIR在病理生理条件下通过调节干扰素-γ的产生来维持骨骼的动态平衡。DCIR缺乏增加了股骨的骨体积，并导致关节的异常骨化，而这些症状在Rag2(-/-)DCIR(-/-)小鼠中被消除。DciR(-/-)小鼠的淋巴和关节中聚集了产生干扰素-γ的T细胞，纯化的DciR(-/-)DC促进了干扰素-γ(+)T细胞的分化。在没有干扰素-γ的情况下，关节僵硬的改变和骨体积的增加受到抑制。因此，干扰素-γ是一种阳性的软骨和成骨因子，而DCIR是骨代谢的重要调节因子；因此，这两种因子都是针对骨代谢疾病治疗的潜在靶点。
Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor mainly expressed in DCs. Dcir(-/-) mice spontaneously develop autoimmune enthesitis and ankylosis accompanied by fibrocartilage proliferation and ectopic ossification. However, the mechanisms of new bone/cartilage formation in Dcir(-/-) mice remain to be elucidated. In this study, we show that DCIR maintains bone homeostasis by regulating IFN-gamma production under pathophysiological conditions. DCIR deficiency increased bone volume in femurs and caused aberrant ossification in joints, whereas these symptoms were abolished in Rag2(-/-) Dcir(-/-) mice. IFN-gamma producing T cells accumulated in lymph nodes and joints of Dcir(-/-) mice, and purified Dcir(-/-) DCs enhanced IFN-gamma(+) T cell differentiation. The ankylotic changes and bone volume increase were suppressed in the absence of IFN-gamma. Thus, IFN-gamma is a positive chondrogenic and osteoblastogenic factor, and DCIR is a crucial regulator of bone metabolism; consequently, both factors are potential targets for therapies directed against bone metabolic diseases.