Magnesium sensing via LFA-1 regulates CD8+ T cell effector function
Details
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State: Public
Version: Final published version
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UNIL restricted access
State: Public
Version: Final published version
License: Not specified
Serval ID
serval:BIB_88810074314B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Magnesium sensing via LFA-1 regulates CD8+ T cell effector function
Journal
Cell
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Publication state
Published
Issued date
17/02/2022
Peer-reviewed
Oui
Volume
185
Number
4
Pages
585-602.e29
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Abstract
The relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8 <sup>+</sup> T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function. Clinically, low serum magnesium levels were associated with more rapid disease progression and shorter overall survival in CAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporates information on the composition of the microenvironment as a determinant of outside-in signaling activity. These findings conceptually link co-stimulation and nutrient sensing and point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.
Keywords
Animals, Bacterial Infections/immunology, CD8-Positive T-Lymphocytes/immunology, Caloric Restriction, Cell Line, Tumor, Cytotoxicity, Immunologic, HEK293 Cells, Humans, Immunologic Memory, Immunological Synapses/metabolism, Immunotherapy, Lymphocyte Activation/immunology, Lymphocyte Function-Associated Antigen-1/metabolism, MAP Kinase Signaling System, Magnesium/administration & dosage, Magnesium/metabolism, Male, Mice, Inbred C57BL, Neoplasms/immunology, Neoplasms/pathology, Neoplasms/therapy, Phenotype, Phosphorylation, Proto-Oncogene Proteins c-jun/metabolism, CAR T cells, Mg2+, T cell engaging antibodies, co-stimulation/LFA-1, immune control, integration of microenvironment and T cell function, magnesium, memory CD8 T cells, microenvironment, tumor-specific T cells
Pubmed
Web of science
Create date
31/01/2022 11:51
Last modification date
04/04/2024 6:11