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
Affiliations
Wenji Piao
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Yanbao Xiong
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Lushen Li
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Vikas Saxena
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Kile D. Smith
Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
Keli L. Hippen
Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
Christina Paluskievicz
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Marina Willsonshirkey
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA
Bruce R. Blazar
Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, MN 55455, USA
Reza Abdi
Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Jonathan S. Bromberg
Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; Corresponding author
Summary: 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. : Piao et al. demonstrate that Tregs condition lymphatic endothelial cells (LECs) to be more permissive for the transendothelial migration (TEM) of other leukocytes. Activation of Toll-like receptor 2 on Tregs during inflammation specifically augments Treg LTα1β2 expression to intensify LTβR signaling in LECs for enhanced immune cell TEM. Keywords: regulatory T cells, lymphatic endothelial cells, Toll-like receptor 2, lymphotoxin, transendothelial migration
