Crosstalk Between the Spleen and Other Organs/Systems: Downstream Signaling Events

The aim of this review was to gather pieces of information from available critically evaluated published articles concerning any interplay in which the spleen could be involved. For many years, the spleen has been alleged as an unnecessary biological structure, even though splenomegaly is an objective finding of many illnesses. Indeed, the previous opinion has been completely changed. In fact, the spleen is not a passive participant in or a simple bystander to a relationship that exists between the immune system and other organs. Recently, it has been evidenced in many preclinical and clinical studies that there are close associations between the spleen and other parts of the body, leading to various spleen–organ axes. Among them, the gut–spleen axis, the liver–spleen axis, the gut–spleen–skin axis, the brain–spleen axis, and the cardio-splenic axis are the most explored and present in the medical literature. Such recent sources of evidence have led to revolutionary new ideas being developed about the spleen. What is more, these observations may enable the identification of novel therapeutic strategies targeted at various current diseases. The time has come to make clear that the spleen is not a superfluous body part, while health system operators and physicians should pay more attention to this organ. Indeed, much work remains to be performed to assess further roles that this biological structure could play.