Bone Abstracts

Chronic inflammatory diseases are characterized by a bone destruction mediated by an increased osteoclast (OCL) activity. OCLs are phagocytic cells arising from the myeloid lineage. Indeed, OCLs derive from monocytes (MN-OCLs) and, in an inflammatory context, they also derive from dendritic cells (DC-OCLs). Despite this origin, their role in the immune responses is still unclear. OCLs in steady state have been reported to act as antigen-presenting cells that activate CD8⁺ regulatory T cells, revealing an immune suppressive function, but such function has never been studied in an inflammatory context.

Our aim was to address the effect of OCLs from different origin on CD4⁺ T cell responses. We set up a unique procedure to purify OCLs on a cell sorter to analyze OCL specific immune function. Working with pure OCL populations, we showed that MN-OCLs and DC-OCLs have the same capacity to process and present antigens. On the other hand, DC-OCLs express high levels of inflammatory cytokines; they efficiently attract CD4⁺ cells, and induce their differentiation into TNFα-producing T cells. In contrast, MN-OCLs are not efficient in attracting CD4⁺ T cells; they induce their differentiation into regulatory T (Treg) cells and express higher levels of immunosuppressive IL-10. These results were confirmed using a murine model of colitis associated with an overactivation of OCLs, the Rag1^−/− mice transferred with naive CD4⁺ T cells. As MN-OCLs, OCLs from control mice induce CD4⁺ T-reg cells, whereas those from colitic mice have the same inflammatory properties than DC-OCLs. Our results demonstrate that MN-OCLs are related with the BM tolerance in steady state, probably avoiding self-reactivity against the peptides continuously produced during bone resorption. In contrast, under inflammatory conditions DC-OCLs may induce inflammatory or autoimmune responses and participate to an amplification loop between bone destruction and inflammation.