Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment

Jarish N. Cohen, Eric F. Tewalt, Sherin J. Rouhani, Erica L. Buonomo, Amber N. Bruce, Xiaojiang Xu, Stefan Bekiranov, Yang Xin Fu, Victor H. Engelhard

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42 Scopus citations

Abstract

Peripheral self-tolerance eliminates lymphocytes specific for tissue-specific antigens not encountered in the thymus. Recently, we demonstrated that lymphatic endothelial cells in mice directly express peripheral tissue antigens, including tyrosinase, and induce deletion of specific CD8 T cells via Programmed Death Ligand-1 (PD-L1). Here, we demonstrate that high-level expression of peripheral tissue antigens and PD-L1 is confined to lymphatic endothelial cells in lymph nodes, as opposed to tissue (diaphragm and colon) lymphatics. Lymphatic endothelial cells in the lymph node medullary sinus express the highest levels of peripheral tissue antigens and PD-L1, and are the only subpopulation that expresses tyrosinase epitope. The representation of lymphatic endothelial cells in the medullary sinus expressing high-level PD-L1, which is necessary for normal CD8 T cell deletion kinetics, is controlled by lymphotoxin-β receptor signaling and B cells. Lymphatic endothelial cells from neonatal mice do not express high-level PD-L1 or present tyrosinase epitope. This work uncovers a critical role for the lymph node microenvironment in endowing lymphatic endothelial cells with potent tolerogenic properties.

Original languageEnglish (US)
Article numbere87740
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 4 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Cohen, J. N., Tewalt, E. F., Rouhani, S. J., Buonomo, E. L., Bruce, A. N., Xu, X., Bekiranov, S., Fu, Y. X., & Engelhard, V. H. (2014). Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment. PloS one, 9(2), [e87740]. https://doi.org/10.1371/journal.pone.0087740