B7-DC/PD-L2 cross-linking induces NF-κB-dependent protection of dendritic cells from cell death

Suresh Radhakrishnan, Loc T. Nguyen, Bogoljub Ciric, Virginia P. Van Keulen, Larry R. Pease

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Cross-linking cell surface molecules with IgM Abs is a specific approach for activating cells in vitro or in vivo. Dendritic cells (DC) activated with a human B7-DC (PD-L2)-specific IgM Ab can induce strong antitumor responses and block inflammatory airway disease in experimental models, yet the Ab-mediated molecular events promoting these responses remain unclear. Analysis of human or mouse DC treated with the B7-DC cross-linking Ab revealed PI3K-dependent phosphorylation of AKT accompanied by mobilization of NF-κB. Ab-activated DC up-regulated expression of cytokine and chemokine genes in an NF-κB-dependent manner. Importantly, PI3K→AKT→NF-κB activation was found to be indispensable for B7-DC cross-linking Ab-mediated protection of DC from cell death caused by cytokine withdrawal. Although other DC activators similarly protect DC from cell death, a synergy between cross-linking B7-DC and ligating RANK was observed. The parallel signaling events induced in human and mouse DC demonstrate that activation of cells using IgM Ab results in a response governed by a common mechanism and support the hypothesis that B7-DC cross-linking using this Ab may provide beneficial therapeutic immune modulation in human patients similar to those seen in animal models.

Original languageEnglish (US)
Pages (from-to)1426-1432
Number of pages7
JournalJournal of Immunology
Volume178
Issue number3
DOIs
StatePublished - Feb 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'B7-DC/PD-L2 cross-linking induces NF-κB-dependent protection of dendritic cells from cell death'. Together they form a unique fingerprint.

  • Cite this