Title

Targeting dendritic cell signaling to regulate the response to immunization

UMMS Affiliation

Program in Molecular Medicine

Date

3-15-2008

Document Type

Article

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Hematology | Immunity | Molecular Biology

Abstract

Dendritic cells (DCs) are key regulators of the immune system; they capture antigens and then can either stimulate an immune response or induce tolerance. Our aim was to activate individual DC signaling pathways to regulate the immune response. We therefore expressed constitutive activators of mitogen-activated protein kinase (MAPK) pathways or the interferon pathway, together with tumor antigens, using lentivectors. Triggering of p38 activated DCs substantially enhanced the antitumor immune response and prolonged survival of tumor-bearing mice. Activation of extracellular signal-regulated kinase (ERK) increased TGF-beta expression while expression of a constitutively activated interferon regulatory factor-3 (IRF3) stimulated IL-10 secretion by DCs. ERK and IRF3 suppressed the immune response and stimulated expansion of regulatory T cells. These results provide a toolkit to regulate immune responses to viral vector or DC immunization; vaccine responses to foreign or tumor antigens can be enhanced and harmful responses to self-antigens or introduced transgenes can be reduced.

Rights and Permissions

Citation: Blood. 2008 Mar 15;111(6):3050-61. doi: 10.1182/blood-2007-11-122408. Epub 2008 Jan 7.. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

18180378