Ca2+ transients on the T cell surface trigger rapid integrin activation in a timescale of seconds

Yue Li, ShiHui Wang, YouHua Zhang, ZhaoYuan Liu, YunZhe Zheng, Kun Zhang, ShiYang Chen, XiaoYing Lv, MengWen Huang, XingChao Pan, YaJuan Zheng, MengYa Yuan, GaoXiang Ge, Yi Arial Zeng, ChangDong Lin () and JianFeng Chen ()
Additional contact information
Yue Li: Chinese Academy of Sciences
ShiHui Wang: Chinese Academy of Sciences
YouHua Zhang: Tongji University
ZhaoYuan Liu: Chinese Academy of Sciences
YunZhe Zheng: Chinese Academy of Sciences
Kun Zhang: Chinese Academy of Sciences
ShiYang Chen: University of Chinese Academy of Sciences
XiaoYing Lv: Tongji University
MengWen Huang: University of Chinese Academy of Sciences
XingChao Pan: Chinese Academy of Sciences
YaJuan Zheng: Chinese Academy of Sciences
MengYa Yuan: Chinese Academy of Sciences
GaoXiang Ge: Chinese Academy of Sciences
Yi Arial Zeng: Chinese Academy of Sciences
ChangDong Lin: Tongji University
JianFeng Chen: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-50464-0

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