Figure 6.

(Color online) Origin of the osteoimmune system in evolution. The bone and immune systems became linked during the course of vertebrate evolution. When aquatic vertebrates moved onto land, the skeletal system adapted to the need to support locomotive activity in the terrestrial environment. At the same time, the immune system rapidly evolved so as to cope with the plethora of terrestrial pathogens, and the location of hematopoiesis moved to the bone marrow to protect HSCs against the higher level of ultraviolet (UV) light exposure on land. Thus, the bone and immune systems developed synchronously, ultimately comprising an osteoimmune system, functioning as a locomotor organ and mineral reservoir as well as a primary lymphoid organ.