Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration
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Date
2020Journal
Cell ReportsPublisher
Elsevier B.V.Type
Article
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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. © 2019 Piao et al.Sponsors
This work was supported by NIH grant RO1 AI062765 to J.S.B., the Maryland Living Legacy Foundation to J.S.B. and W.P., R01 AI126596 and R01 HL141815 to R.A., RO1 CA72669 to B.R.B., and R01 HL11879 and P01 CA 065493 to B.R.B. and K.L.H.Keyword
lymphatic endothelial cellslymphotoxin
regulatory T cells
Toll-like receptor 2
transendothelial migration
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https://www.scopus.com/inward/record.uri?eid=2-s2.0-85078324997&doi=10.1016%2fj.celrep.2019.12.083&partnerID=40&md5=0a53e6924365b48aab98078d25098535; http://hdl.handle.net/10713/11653ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2019.12.083