biostudies-literatureUnknown9(2)Madlmayr AT-lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7, transient receptor potential cation channel subfamily M, member 7, has previously been implicated in cellular Mg2+ homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished activation and influences signaling pathways that guide human TH17 or Treg cell differentiation, following TCR-mediated stimulation. In primary human CD4 T cells and CRISPR-Cas9-engineered Jurkat T cells, inactivation or loss of TRPM7 led to distorted Mg2+ homeostasis and Ca2+ signaling, reduced NFAT translocation, deLife science alliancee202503357https://www.ebi.ac.uk/biostudies/studies/S-EPMC12670122biostudies-literatureTRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.PMC12670122Madlmayr ALewitz DSchedlberger CDietrich AGudermann TWeng MLechner MDuggan MRoss RSperandio MKarner-Hoeger BHacker SHorner KHorgen FDEder JZierler SHaider THoelting KfalseTRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation.T-lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7, transient receptor potential cation channel subfamily M, member 7, has previously been implicated in cellular Mg2+ homeostasis, proliferation, and immune cell modulation. Here, we show that pharmacological and genetic silencing of TRPM7 leads to diminished activation and influences signaling pathways that guide human TH17 or Treg cell differentiation, following TCR-mediated stimulation. In primary human CD4 T cells and CRISPR-Cas9-engineered Jurkat T cells, inactivation or loss of TRPM7 led to distorted Mg2+ homeostasis and Ca2+ signaling, reduced NFAT translocation, de2026-01-01T00:00:00Z2026 Feb2026-06-05T21:04:40.628Z2026-05-21T03:13:04.188ZS-EPMC126701224132617310.26508/lsa.202503357