Magnesium sensing via LFA-1 regulates CD8+ T cell effector function
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Authors
Lötscher, Jonas
Martí i Líndez, Adrià-Arnau
Kirchhammer, Nicole
Cribioli, Elisabetta
Giordano Attianese, Greta Maria Paola
Trefny, Marcel P.
Rothschild, Sacha I.
Strati, Paolo
Künzli, Marco
Lotter, Claudia
Author (Corporation)
Publication date
2022
Typ of student thesis
Course of study
Collections
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Cell
Special issue
DOI of the original publication
Link
Series
Series number
Volume
185
Issue / Number
4
Pages / Duration
585-602.e29
Patent number
Publisher / Publishing institution
Cell Press
Place of publication / Event location
Edition
Version
Programming language
Assignee
Practice partner / Client
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.
Keywords
T cell engaging antibodies, Immune control, Memory CD8 T cells, Microenvironment, Co-stimulation/LFA-1, Integration of microenvironment and T cell function, Tumor-specific T cells
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ISBN
ISSN
0092-8674
1097-4172
1097-4172
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Green
License
Citation
Lötscher, J., Martí i Líndez, A.-A., Kirchhammer, N., Cribioli, E., Giordano Attianese, G. M. P., Trefny, M. P., 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., et al. (2022). Magnesium sensing via LFA-1 regulates CD8+ T cell effector function. Cell, 185(4), 585–602. https://doi.org/10.1016/j.cell.2021.12.039