Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1

Description

Bone destruction relies on interactions between bone and immune cells. Boneresorbing osteoclasts (OCLs) were recently identified as innate immune cells activating T cells toward tolerance or inflammation. Thus, pathological bone destruction not only relies on increased osteoclast differentiation, but also on the presence of inflammatory OCLs (i-OCLs), part of which express Cx3cr1. Here, we investigated the contribution of mouse Cx3cr1 + and Cx3cr1 neg i-OCLs to bone loss. We showed that Cx3cr1 + and Cx3cr1 neg i-OCLs differ considerably in transcriptional and functional aspects. Cx3cr1 neg i-OCLs have a high ability to resorb bone and activate inflammatory CD4 + T cells. Although Cx3cr1 + i-OCLs are associated with inflammation, they resorb less and have in vitro an immune-suppressive effect on Cx3cr1 neg i-OCLs, mediated by PD-L1. Our results provide new insights into i-OCL heterogeneity. They also reveal that different i-OCL subsets may interact to regulate inflammation. This contributes to a better understanding and prevention of inflammatory bone destruction.

Abstract

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