Consistently, it has been demonstrated that estrogens suppress RANKL production not only in osteoblasts but also in T and B cells (120), while the lack of estrogens increases the release of pro-osteoclastogenic cytokines (i.e., TNF-α and RANKL) by activated T cells (121–123) thus indirectly identifying immune cells as additional players in the onset of osteoporosis. The gene discussed is TNFSF11; the disease is osteoporosis.