Regulatory T Cells Condition Lymphatic Endothelia for Enhanced Transendothelial Migration

Wenji Piao, Yanbao Xiong, Lushen Li, Vikas Saxena, Kile D. Smith, Keli L. Hippen, Christina Paluskievicz, Marina Willsonshirkey, Bruce R. Blazar, Reza Abdi, Jonathan S. Bromberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1052-1062.e5
JournalCell reports
Volume30
Issue number4
DOIs
StatePublished - Jan 28 2020

Bibliographical note

Funding Information:
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. We thank Dr. Wei Chao (Department Anesthesiology, UMB) for the TLR2KO mice and Dr. Xiaoxuan Fan from the UMB-Flow Core Facility for his excellent help with flow cell sorting and data analysis.

Publisher Copyright:
© 2019

Keywords

  • Toll-like receptor 2
  • lymphatic endothelial cells
  • lymphotoxin
  • regulatory T cells
  • transendothelial migration

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