{"doi":"10.26508/lsa.202503357","title":"TRPM7 and magnesium orchestrate human CD4 T-cell activation and differentiation","abstract":"T-lymphocyte activation is a crucial process in the regulation of innate and adaptive immune responses. The ion channel-kinase TRPM7, t ransient r eceptor p otential cation channel subfamily M , member 7 , has previously been implicated in cellular Mg 2+ 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 T H 17 or T reg 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 Mg 2+ homeostasis and Ca 2+ signaling, reduced NFAT translocation, decreased IL-2 secretion and altered T H cell differentiation. While the activation of primary human CD4 T cells, as well as in vitro polarization into pro-inflammatory T H 17 cells was critically dependent on TRPM7, the polarization of naïve CD4 T cells into FOXP3 + regulatory T cells was not. Taken together, these results highlight TRPM7 as molecular switch in lymphocyte activation and polarization. Thus, suggesting a therapeutic potential for TRPM7 in numerous T-cell mediated diseases.","journal":"Life Science Alliance","year":2025,"id":549131,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1442803,"name":"Kilian Hoelting","orcid":"0000-0002-6531-273X","position":1,"is_corresponding":false},{"id":1442804,"name":"Birgit Hoeger","orcid":"0000-0001-7491-9405","position":2,"is_corresponding":false},{"id":1443293,"name":"Dorothea Lewitz","orcid":null,"position":3,"is_corresponding":false},{"id":1443294,"name":"Marius Weng","orcid":null,"position":4,"is_corresponding":false},{"id":1443295,"name":"Severin Hacker","orcid":null,"position":5,"is_corresponding":false},{"id":1443296,"name":"Julia Eder","orcid":null,"position":6,"is_corresponding":false},{"id":1443297,"name":"Katharina Hörner","orcid":null,"position":7,"is_corresponding":false},{"id":1443298,"name":"Christine Schedlberger","orcid":null,"position":8,"is_corresponding":false},{"id":1443299,"name":"Tanja Haider","orcid":null,"position":9,"is_corresponding":false},{"id":1443300,"name":"Max Lechner","orcid":null,"position":10,"is_corresponding":false},{"id":1443301,"name":"Michelle Duggan","orcid":null,"position":11,"is_corresponding":false},{"id":1443302,"name":"Rylee Ross","orcid":null,"position":12,"is_corresponding":false},{"id":342113,"name":"F. David Horgen","orcid":"0000-0001-9409-3030","position":13,"is_corresponding":false},{"id":392167,"name":"Markus Sperandio","orcid":"0000-0002-7689-3613","position":14,"is_corresponding":false},{"id":241184,"name":"Alexander Dietrich","orcid":"0000-0002-1168-8707","position":15,"is_corresponding":false},{"id":666319,"name":"Thomas Gudermann","orcid":"0000-0002-0323-7965","position":16,"is_corresponding":false},{"id":666321,"name":"Susanna Zierler","orcid":"0000-0002-4684-0385","position":17,"is_corresponding":false},{"id":1442802,"name":"Anna Madlmayr","orcid":"0000-0002-4518-147X","position":0,"is_corresponding":true}],"reference_count":71,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41326173","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}