%0 Journal Article
%T Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds.
%A Li Y
%A Wang S
%A Zhang Y
%A Liu Z
%A Zheng Y
%A Zhang K
%A Chen S
%A Lv X
%A Huang M
%A Pan X
%A Zheng Y
%A Yuan M
%A Ge G
%A Zeng YA
%A Lin C
%A Chen J
%J Nat Commun
%V 15
%N 1
%D 2024 Jul 20
%M 39033133
%F 17.694
%R 10.1038/s41467-024-50464-0
%X One question in lymphocyte homing is how integrins are rapidly activated to enable immediate arrest of fast rolling lymphocytes upon encountering chemokines at target vascular beds given the slow chemokine-induced integrin inside-out activation. Herein we demonstrate that chemokine CCL25-triggered Ca2+ influx induces T cell membrane-proximal external Ca2+ concentration ([Ca2+]ex) drop in 6 s from physiological concentration 1.2 mM to 0.3 mM, a critical extracellular Ca2+ threshold for inducing αLβ2 activation, triggering rapid αLβ2 activation and T cell arrest before occurrence of αLβ2 inside-out activation. Talin knockdown inhibits the slow inside-out activation of αLβ2 but not [Ca2+]ex drop-triggered αLβ2 quick activation. Blocking Ca2+ influx significantly suppresses T cell rolling-to-arrest transition and homing to skin lesions in a mouse psoriasis model, thus alleviating skin inflammation. [Ca2+]ex decrease-triggered rapid integrin activation bridges the gap between initial chemokine stimulation and slow integrin inside-out activation, ensuring immediate lymphocyte arrest and subsequent diapedesis on the right location.