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

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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
StatePublished - Feb 1 2007

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Dendritic Cells
Cell Death
Immunoglobulin M
Cytokines
Phosphatidylinositol 3-Kinases
Chemokines
Theoretical Models
Animal Models
Phosphorylation

ASJC Scopus subject areas

  • Immunology

Cite this

Radhakrishnan, S., Nguyen, L. T., Ciric, B., Van Keulen, V. P., & Pease, L. R. (2007). B7-DC/PD-L2 cross-linking induces NF-κB-dependent protection of dendritic cells from cell death. Journal of Immunology, 178(3), 1426-1432.

B7-DC/PD-L2 cross-linking induces NF-κB-dependent protection of dendritic cells from cell death. / Radhakrishnan, Suresh; Nguyen, Loc T.; Ciric, Bogoljub; Van Keulen, Virginia P.; Pease, Larry R.

In: Journal of Immunology, Vol. 178, No. 3, 01.02.2007, p. 1426-1432.

Research output: Contribution to journalArticle

Radhakrishnan, S, Nguyen, LT, Ciric, B, Van Keulen, VP & Pease, LR 2007, 'B7-DC/PD-L2 cross-linking induces NF-κB-dependent protection of dendritic cells from cell death', Journal of Immunology, vol. 178, no. 3, pp. 1426-1432.
Radhakrishnan, Suresh ; Nguyen, Loc T. ; Ciric, Bogoljub ; Van Keulen, Virginia P. ; Pease, Larry R. / B7-DC/PD-L2 cross-linking induces NF-κB-dependent protection of dendritic cells from cell death. In: Journal of Immunology. 2007 ; Vol. 178, No. 3. pp. 1426-1432.
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