FIGURE 2.

Immunoregulation by osteoclasts. Under physiological conditions, osteoclasts are considered to be derived from monocyte progenitor cells and exhibit immunomodulatory activities in order to maintain immune tolerance to bone remnants. To do so, osteoclasts induce Treg cells through antigen presentation in MHC-I complexes towards CD8⁺ T cells. Osteoclasts inhibit T cell proliferation, production of inflammatory cytokines, and activation-induced apoptosis through release of soluble mediators. Under inflammatory conditions, osteoclasts are hypothesized to derive from DC and to contribute to immune diseases, including RA. In response to LPS or IFN-γ, osteoclasts produce pro-inflammatory mediators and differentiate naïve T cells into Th1 cells through antigen presentation in MHC-II molecules.