Role of CX3CR1 in osteoclast differentiation in mice. ORIOS_CX3CR1

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