Cutting edge: Role of osteopontin and integrin αv in T cell-mediated anti-inflammatory responses in endotoxemia

Makoto Inoue, Mari L. Shinohara

Research output: Contribution to journalArticlepeer-review

Abstract

The immune system is equipped with mechanisms that downregulate hyperinflammation to avoid collateral damage. We demonstrated recently that unprimed T cells downregulate macrophage TNF production through direct interaction with macrophages in the spleen during LPS endotoxemia. How T cell migration toward macrophages occurs upon LPS injection is still not clear. In this study, we demonstrate that secreted osteopontin (sOPN) plays a role in the T cell migration to initiate the suppression of hyperinflammation during endotoxemia. Osteopontin levels in splenic macrophages were upregulated 2 h after LPS treatment, whereas T cell migration toward macrophages was observed 3 h after treatment. Neutralization of sOPN and blockade of its receptor, integrin αv, significantly inhibited CD4+ T cell migration and increased susceptibility to endotoxemia. Our study demonstrates that the sOPN/ integrin αv axis, which induces T cell chemotaxis toward macrophages, is critical for suppressing hyperinflammation during the first 3 h of endotoxemia.

Original languageEnglish (US)
Pages (from-to)5595-5598
Number of pages4
JournalJournal of Immunology
Volume194
Issue number12
DOIs
StatePublished - Jun 15 2015
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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