Role of CX3CR1 in osteoclast differentiation in mice

Inflammatory bone destruction involves reciprocal interactions between bone and immune cells. Indeed, bone-resorbing osteoclasts (OCLs) are also antigen-presenting cells activating T-cells toward tolerance or inflammation. Pathological bone destruction is characterized by the emergence of inflammatory OCLs (i-OCLs) of which a part express CX3CR1. However, the contribution of CX3CR1+ and CX3CR1neg i-OCLs to inflammatory bone loss is not fully elucidated. Here we showed that CX3CR1+ and CX3CR1neg i-OCLs differ considerably in their bone resorptive and immune functions. While CX3CR1neg i-OCLs resorb bone and activate inflammatory CD4+ T cells more efficiently, CX3CR1+ i-OCLs have lower bone resorption activity and are more prone to immune suppression due to their high expression of immunosuppressive genes such as PD-L1. Moreover, CX3CR1+ i-OCLs suppress the inflammatory activity of CX3CR1neg i-OCLs. These new insights into OCLs heterogeneity and the interaction between different OCL subsets contribute to a better understanding and prevention of inflammatory bone loss. This study has been published at DOI: https://doi.org/10.7554/eLife.54493

炎症性骨破坏涉及骨细胞与免疫细胞的双向相互作用。事实上，骨吸收破骨细胞（osteoclasts, OCLs）同时也是抗原呈递细胞，可激活T细胞以介导免疫耐受或炎症反应。病理性骨破坏以炎症性破骨细胞（inflammatory OCLs, i-OCLs）的出现为特征，其中部分亚群表达CX3CR1（C-X3-C趋化因子受体1）。然而，CX3CR1阳性与CX3CR1阴性的炎症性破骨细胞对炎症性骨丢失的贡献尚未完全阐明。本研究发现，CX3CR1阳性与CX3CR1阴性的炎症性破骨细胞在骨吸收功能与免疫功能上存在显著差异：CX3CR1阴性炎症性破骨细胞可更高效地吸收骨组织并激活炎症性CD4阳性T细胞；而CX3CR1阳性炎症性破骨细胞的骨吸收活性更低，且因高表达程序性死亡受体配体1（PD-L1）等免疫抑制基因，更易介导免疫抑制。此外，CX3CR1阳性炎症性破骨细胞还可抑制CX3CR1阴性炎症性破骨细胞的炎症活性。这些针对破骨细胞异质性及不同破骨细胞亚群间相互作用的新认知，有助于更深入地理解炎症性骨丢失并为其防治提供新思路。本研究已发表于DOI：https://doi.org/10.7554/eLife.54493