Dies ist nicht die neueste Version dieses Items. Die neueste Version finden Sie hier.
Magnesium sensing via LFA-1 regulates CD8+ T cell effector function
Vorschaubild nicht verfügbar
Publikationsdatum
2022
Autor:innen
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
Zeitschriftentitel
ISSN der Zeitschrift
Bandtitel
Verlag
Elsevier
Zusammenfassung
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.
Beschreibung
Schlagwörter
immune control, memory CD8 T cells, microenvironment, Mg2+, co-stimulation/LFA-1, integration of microenvironment and T cell function, tumor-specific T cells, T cell engaging antibodies
Zitierform
DOI der Originalpublikation
Zitation
LÖTSCHER, Jonas, Adrià-Arnau MARTÍ I LÍNDEZ, Nicole KIRCHHAMMER, Elisabetta CRIBIOLI, Greta Maria Paola GIORDANO ATTIANESE, Marcel P. TREFNY, Sacha I. ROTHSCHILD, Paolo STRATI, Marco KÜNZLI, Claudia LOTTER, Susanne H. SCHENK, Philippe DEHIO, Jordan LÖLIGER, Ludivine LITZLER, David SCHREINER, Victoria KOCH, Nicolas PAGE, Dahye LEE, Jasmin GRÄHLERT, Dmitry KUZMIN, Anne-Valérie BURGENER, Doron MERKLER, Miklos PLESS, Maria L. BALMER, Walter REITH, Jörg HUWYLER, Melita IRVING, Carolyn G. KING, Alfred ZIPPELIUS, Christoph HESS und Markus LENZ, 2022. Magnesium sensing via LFA-1 regulates CD8+ T cell effector function. Cell. 2022. Bd. 185, Nr. 4, S. 585–602.e29. DOI 10.1016/j.cell.2021.12.039. Verfügbar unter: https://doi.org/10.1016/j.cell.2021.12.039