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

    112 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

    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