Endothelial heparan sulfate controls chemokine presentation in recruitment of lymphocytes and dendritic cells to lymph nodes

Xingfeng Bao, E. Ashley Moseman, Hideo Saito, Bronislawa Petryanik, Aude Thiriot, Shingo Hatakeyama, Yuki Ito, Hiroto Kawashima, Yu Yamaguchi, John B. Lowe, Ulrich H. von Andrian, Minoru Fukuda

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)

Abstract

Heparan sulfate can bind several adhesion molecules involved in lymphocyte trafficking. However, the in vivo function of endothelial heparan sulfate in lymphocyte homing and stimulation of the immune response has not been elucidated. Here, we generated mutant mice deficient in the enzyme Ext1, which is required for heparan sulfate synthesis, in a Tek-dependent and inducible manner. Chemokine presentation was diminished in the mutant mice, causing the lack of appropriate integrin-mediated adhesion, and resulted in a marked decrease in lymphocyte sticking to high endothelial venules and in recruitment of resident dendritic cells through lymphatic vessels to the lymph nodes. As a consequence, mutant mice displayed a severe impairment in lymphocyte homing and a compromised contact hypersensitivity response. By contrast, lymphocyte rolling was increased because of loss of electrostatic repulsion by heparan sulfate. These results demonstrate critical roles of endothelial heparan sulfate in immune surveillance and immune response generation.

Original languageEnglish
Pages (from-to)817-829
Number of pages13
JournalImmunity
Volume33
Issue number5
DOIs
Publication statusPublished - 2010 Nov 24
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Endothelial heparan sulfate controls chemokine presentation in recruitment of lymphocytes and dendritic cells to lymph nodes'. Together they form a unique fingerprint.

Cite this