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Magnesium sensing via LFA-1 regulates CD8+ T cell effector function
dc.accessRights | Anonymous | * |
dc.contributor.author | Lötscher, Jonas | |
dc.contributor.author | Martí i Líndez, Adrià-Arnau | |
dc.contributor.author | Kirchhammer, Nicole | |
dc.contributor.author | Cribioli, Elisabetta | |
dc.contributor.author | Giordano Attianese, Greta Maria Paola | |
dc.contributor.author | Trefny, Marcel P. | |
dc.contributor.author | Rothschild, Sacha I. | |
dc.contributor.author | Strati, Paolo | |
dc.contributor.author | Künzli, Marco | |
dc.contributor.author | Lotter, Claudia | |
dc.contributor.author | Schenk, Susanne H. | |
dc.contributor.author | Dehio, Philippe | |
dc.contributor.author | Löliger, Jordan | |
dc.contributor.author | Litzler, Ludivine | |
dc.contributor.author | Schreiner, David | |
dc.contributor.author | Koch, Victoria | |
dc.contributor.author | Page, Nicolas | |
dc.contributor.author | Lee, Dahye | |
dc.contributor.author | Grählert, Jasmin | |
dc.contributor.author | Kuzmin, Dmitry | |
dc.contributor.author | Burgener, Anne-Valérie | |
dc.contributor.author | Merkler, Doron | |
dc.contributor.author | Pless, Miklos | |
dc.contributor.author | Balmer, Maria L. | |
dc.contributor.author | Reith, Walter | |
dc.contributor.author | Huwyler, Jörg | |
dc.contributor.author | Irving, Melita | |
dc.contributor.author | King, Carolyn G. | |
dc.contributor.author | Zippelius, Alfred | |
dc.contributor.author | Hess, Christoph | |
dc.contributor.author | Lenz, Markus | |
dc.date.accessioned | 2022-10-12T10:14:16Z | |
dc.date.available | 2022-10-12T10:14:16Z | |
dc.date.issued | 2022 | |
dc.description.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+ 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. | en_US |
dc.identifier.doi | 10.1016/j.cell.2021.12.039 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.uri | https://doi.org/10.1016/j.cell.2021.12.039 | |
dc.identifier.uri | https://irf.fhnw.ch/handle/11654/33940.1 | |
dc.issue | 4 | en_US |
dc.language.iso | en | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.ispartof | Cell | en_US |
dc.subject | immune control | en_US |
dc.subject | memory CD8 T cells | en_US |
dc.subject | microenvironment | en_US |
dc.subject | Mg2+ | en_US |
dc.subject | co-stimulation/LFA-1 | en_US |
dc.subject | integration of microenvironment and T cell function | en_US |
dc.subject | tumor-specific T cells | en_US |
dc.subject | T cell engaging antibodies | en_US |
dc.subject.ddc | 500 - Naturwissenschaften | en_US |
dc.title | Magnesium sensing via LFA-1 regulates CD8+ T cell effector function | en_US |
dc.type | 01A - Beitrag in wissenschaftlicher Zeitschrift | * |
dc.volume | 185 | en_US |
fhnw.InventedHere | Yes | en_US |
fhnw.IsStudentsWork | no | en_US |
fhnw.ReviewType | Anonymous ex ante peer review of a complete publication | en_US |
fhnw.openAccessCategory | Green | |
fhnw.pagination | 585-602.e29 | en_US |
fhnw.publicationState | Published | en_US |
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