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2017 ; 10
(469
): ä Nephropedia Template TP
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Cytoskeletal adaptivity regulates T cell receptor signaling
#MMPMID28270556
Thauland TJ
; Hu KH
; Bruce MA
; Butte MJ
Sci Signal
2017[Mar]; 10
(469
): ä PMID28270556
show ga
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 naïve (unstimulated) T cells.
Using atomic force microscopy and quantitative confocal microscopy, we found that
naïve T cells had a mechanically stiffer cortical cytoskeleton than that of
effector cells, which resulted in naïve 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.
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