Magnesium sensing via LFA-1 regulates CD8<sup>+</sup> T cell effector function.

Details

Serval ID
serval:BIB_88810074314B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Magnesium sensing via LFA-1 regulates CD8<sup>+</sup> T cell effector function.
Journal
Cell
Author(s)
Lötscher J., Martí I Líndez A.A., Kirchhammer N., Cribioli E., Giordano Attianese GMP, Trefny M.P., Lenz M., Rothschild S.I., Strati P., Künzli M., Lotter C., Schenk S.H., Dehio P., Löliger J., Litzler L., Schreiner D., Koch V., Page N., Lee D., Grählert J., Kuzmin D., Burgener A.V., Merkler D., Pless M., Balmer M.L., Reith W., Huwyler J., Irving M., King C.G., Zippelius A., Hess C.
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
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 12:51
Last modification date
23/04/2022 6:35
Usage data