The role of Mg2+ in immune cells

The physiological and clinical relevance of Mg2+ has evolved over the last decades. The molecular identification of multiple Mg2+ transporters (Acdp2, MagT1, Mrs2, Paracellin-1, SLC41A1, SLC41A2, TRPM6 and TRPM7) and their biophysical characterization in recent years has improved our understanding of Mg2+ homeostasis regulation and has provided a basis for investigating the role of Mg2+ in the immune system. Deletions and mutations of Mg2+ transporters produce severe phenotypes with more systemic symptoms than those seen with Ca2+ channel deletions, which tend to be more specific and less profound. Deficiency of the Mg2+ permeable ion channels TRPM6 or TRPM7 in mice is lethal at embryonic day 12.5 or at day 6.5, respectively, and, even more surprisingly, chicken DT40 B cells lacking TRPM7 die after 24–48 h. Recent progress made in Mg2+ research has helped to define underlying mechanisms of two hereditary diseases, human Hypomagnesemia (TRPM6 deletion) and X-chromosomal immunodeficiency (MagT1 deletion), and has revealed a potential new role for Mg2+ as a second messenger. Future elucidation of human Mg2+ transporters (Mrs2, SLC41A1, SLC41A2, TRPM7) expressed in immunocytes, beyond MagT1 and TRPM6, will widen our knowledge about the potential role of Mg2+ in the activation of the immune response.