Divalent cation signaling in immune cells

•Ca2+, Mg2+, and Zn2+ are signaling cations with interconnected signal networks.•Cation signaling is essential for immunity and defects underlie immune diseases.•Mechanisms of Mg2+ and Zn2+ mobilization and effectors require further definition.•Modulation of ion signaling may lead to novel therapies for immune diseases.

Divalent cations of two alkaline earth metals Ca2+ and Mg2+ and the transition metal Zn2+ play vital roles in the immune system, and several immune disorders are associated with disturbances of their function. Until recently only Ca2+ was considered to serve as a second messenger. However, signaling roles for Mg2+ and Zn2+ have been recently described, leading to a reevaluation of their role as potential second messengers. We review here the roles of these cations as second messengers in light of recent advances in Ca2+, Mg2+, and Zn2+ signaling in the immune system. Developing a better understanding of these signaling cations may lead to new therapeutic strategies for immune disorders.