Figure 1. The RANKL and Cytokine Interactions Network (RACIN) proposed during periodontal pathogenesis (Teng et al., 2005). Local innate immune cells (i.e., dendritic cells, macrophages, or other antigen-presenting cells) encounter periodontal pathogens and pick up and present critical microbial antigens/peptides to prime naïve T-cells in the periodontal micro-environment, where RANKL-expressing Th1 vs. Th2 cells become activated by secreting IFN- and TNF- vs. IL-10 and TGF-ß cytokines. There may exist cross-talk or feedback regulation between the interacting cytokines in the micro-environment that modulate or influence the resulting RANKL-mediated periodontal osteoclastogenesis and tissue inflammation or anti-inflammatory processes associated with tissue repair (i.e., via fibroblasts). Note that the overall contribution of periodontal/mucosal resident cells or mesenchymal tissues to RANKL/OPG-mediated osteoclastogenesis is not described here, due to the lack of in vivo data.