| First Author | L?tscher J | Year | 2022 |
| Journal | Cell | Volume | 185 |
| Issue | 4 | Pages | 585-602.e29 |
| PubMed ID | 35051368 | Mgi Jnum | J:336914 |
| Mgi Id | MGI:6874732 | Doi | 10.1016/j.cell.2021.12.039 |
| Citation | Lotscher J, et al. (2022) Magnesium sensing via LFA-1 regulates CD8(+) T cell effector function. Cell 185(4):585-602.e29 |
| abstractText | 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. |
