| First Author | Thauland TJ | Year | 2017 |
| Journal | Sci Signal | Volume | 10 |
| Issue | 469 | PubMed ID | 28270556 |
| Mgi Jnum | J:259841 | Mgi Id | MGI:6142777 |
| Doi | 10.1126/scisignal.aah3737 | Citation | Thauland TJ, et al. (2017) Cytoskeletal adaptivity regulates T cell receptor signaling. Sci Signal 10(469) |
| abstractText | The factors that govern T cell activation control the initiation and progression of adaptive immune responses. T cells recognize their cognate antigen on the surface of antigen-presenting cells (APCs) through the T cell receptor, which results in the formation of a contact region (immune synapse) between the two cells and the activation of the T cells. Activated T cells proliferate and differentiate into effector T cells that secrete cytokines, provide help to B cells, and kill target cells. We asked whether the actin cytoskeleton governs differences in signaling in effector T cells versus naive (unstimulated) T cells. Using atomic force microscopy and quantitative confocal microscopy, we found that naive T cells had a mechanically stiffer cortical cytoskeleton than that of effector cells, which resulted in naive cells forming smaller immune synapses with APCs. This suggests that the cytoskeletal stiffness of the T cell before it undergoes antigen stimulation predicts its subsequent dynamic engagement with APCs and its activation potential. Cytoskeletal rigidity depended on the activity of the actin-severing enzyme cofilin through a pathway requiring the small guanosine triphosphatase RhoA and the kinases ROCK (Rho-activated kinase) and LIMK. These findings suggest that the baseline cytoskeletal state controls T cell responses and that the underlying pathway could be a therapeutic target for modulating adaptive immunity. |
