| First Author | Morelli AE | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 10 | Pages | 3448-3465.e8 |
| PubMed ID | 32160549 | Mgi Jnum | J:287651 |
| Mgi Id | MGI:6416789 | Doi | 10.1016/j.celrep.2020.02.054 |
| Citation | Morelli AE, et al. (2020) Neurokinin-1 Receptor Signaling Is Required for Efficient Ca(2+) Flux in T-Cell-Receptor-Activated T Cells. Cell Rep 30(10):3448-3465.e8 |
| abstractText | Efficient Ca(2+) flux induced during cognate T cell activation requires signaling the T cell receptor (TCR) and unidentified G-protein-coupled receptors (GPCRs). T cells express the neurokinin-1 receptor (NK1R), a GPCR that mediates Ca(2+) flux in excitable and non-excitable cells. However, the role of the NK1R in TCR signaling remains unknown. We show that the NK1R and its agonists, the neuropeptides substance P and hemokinin-1, co-localize within the immune synapse during cognate activation of T cells. Simultaneous TCR and NK1R stimulation is necessary for efficient Ca(2+) flux and Ca(2+)-dependent signaling that sustains the survival of activated T cells and helper 1 (Th1) and Th17 bias. In a model of contact dermatitis, mice with T cells deficient in NK1R or its agonists exhibit impaired cellular immunity, due to high mortality of activated T cells. We demonstrate an effect of the NK1R in T cells that is relevant for immunotherapies based on pro-inflammatory neuropeptides and its receptors. |
