TY - JOUR TI - Dissecting the phenotypic and functional heterogeneity of mouse inflammatory osteoclasts by the expression of Cx3cr1 AU - Madel, Maria-Bernadette AU - Ibáñez, Lidia AU - Ciucci, Thomas AU - Halper, Julia AU - Rouleau, Matthieu AU - Boutin, Antoine AU - Hue, Christophe AU - Duroux-Richard, Isabelle AU - Apparailly, Florence AU - Garchon, Henri-Jean AU - Wakkach, Abdelilah AU - Blin-Wakkach, Claudine A2 - Vunjak-Novakovic, Gordana A2 - Cheah, Kathryn Song Eng VL - 9 PY - 2020 DA - 2020/05/13 SP - e54493 C1 - eLife 2020;9:e54493 DO - 10.7554/eLife.54493 UR - https://doi.org/10.7554/eLife.54493 AB - Bone destruction relies on interactions between bone and immune cells. Bone-resorbing 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 Cx3cr1neg i-OCLs to bone loss. We showed that Cx3cr1+ and Cx3cr1neg i-OCLs differ considerably in transcriptional and functional aspects. Cx3cr1neg 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 Cx3cr1neg 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. KW - osteoclast KW - osteoporosis KW - osteoimmunology KW - bone destruction KW - inflammation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -