TY - JOUR
T1 - Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration
AU - Piao, Wenji
AU - Xiong, Yanbao
AU - Li, Lushen
AU - Saxena, Vikas
AU - Smith, Kile D.
AU - Hippen, Keli L.
AU - Paluskievicz, Christina
AU - Willsonshirkey, Marina
AU - Blazar, Bruce R.
AU - Abdi, Reza
AU - Bromberg, Jonathan S.
N1 - Publisher Copyright:
© 2019
PY - 2020/1/28
Y1 - 2020/1/28
N2 - Regulatory T cells (Tregs) express high levels of cell surface lymphotoxin alpha beta (LTα1β2) to activate the LT beta receptor (LTβR) on the lymphatic endothelial cells (LECs), modulating LEC adhesion molecules, intercellular junctions, and chemokines. We demonstrate a role for Tregs through this pathway to condition the permissiveness of lymphatic endothelia for transendothelial migration (TEM), thus gating leukocyte traffic. Human Tregs share the same property with murine Tregs. Activation of TLR2 on Tregs during inflammation specifically augments LTα1β2-LTβR signaling, which further enhances the permissiveness of LECs to facilitate TEM. The conditioning of endothelia may promote the resolution of inflammation by directing leukocytes out of tissues to lymphatic vessels and draining lymph nodes (dLNs). Thus, Tregs interact with lymphatic endothelia under homeostasis and inflammation and dictate endothelial permissiveness and gating mechanisms for subsequent leukocyte migration through endothelial barriers.
AB - Regulatory T cells (Tregs) express high levels of cell surface lymphotoxin alpha beta (LTα1β2) to activate the LT beta receptor (LTβR) on the lymphatic endothelial cells (LECs), modulating LEC adhesion molecules, intercellular junctions, and chemokines. We demonstrate a role for Tregs through this pathway to condition the permissiveness of lymphatic endothelia for transendothelial migration (TEM), thus gating leukocyte traffic. Human Tregs share the same property with murine Tregs. Activation of TLR2 on Tregs during inflammation specifically augments LTα1β2-LTβR signaling, which further enhances the permissiveness of LECs to facilitate TEM. The conditioning of endothelia may promote the resolution of inflammation by directing leukocytes out of tissues to lymphatic vessels and draining lymph nodes (dLNs). Thus, Tregs interact with lymphatic endothelia under homeostasis and inflammation and dictate endothelial permissiveness and gating mechanisms for subsequent leukocyte migration through endothelial barriers.
KW - Toll-like receptor 2
KW - lymphatic endothelial cells
KW - lymphotoxin
KW - regulatory T cells
KW - transendothelial migration
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U2 - 10.1016/j.celrep.2019.12.083
DO - 10.1016/j.celrep.2019.12.083
M3 - Article
C2 - 31995749
AN - SCOPUS:85078324997
SN - 2211-1247
VL - 30
SP - 1052-1062.e5
JO - Cell reports
JF - Cell reports
IS - 4
ER -