A-kinase anchoring in Dendritic cells is required for antigen presentation

Robynn V. Schillace, Casey L. Miller, Neal Pisenti, Jeff E. Grotzke, Gwendolyn M. Swarbrick, David Lewinsohn, Daniel Carr

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Dendritic cells (DC) are the most potent antigen presenting cells (APC) of the immune system. Prostaglandin E2, cyclic AMP, and protein kinase A (PKA) have all been shown to regulate DC maturation and activity. In other cells, the ability to these molecules to convey their signals has been shown to be dependent on A-kinase achoring proteins (AKAPS). Here we present evidence for the existence and functional importance of AKAPs in human DC. Methodolog/Principal Findings: Using immunofluorescence and/or western analyses we identify AKAP79, AKAP149, AKAP95, AKAP LBC and Ezrin: We also demonstrate by western analysis that expression of AKAP79, AKAP149 and RII are upregulated with DC differentiation and maturation. We establish the functional importance of PKA anchoring in multiple aspects of DC biology using the anchoring inhibitor peptides Ht31 and AKAP-15. Incubation of protein or peptide antigen loaded DC with Ht31 or AKAP-IS results in a 30-50% decrease in antigen presentation as measured by IFN-γ production from antigen specific CD4+ T cells. Incubation of LPS treated DC with Ht31 results in 80% inhibition of TNF-α and IL-10 production. Ht31 slightly decreases the expression of CD18 and CD11a and CD11b; slightly increases the basal expression of CD83, dramatically decreases the LPS stimulated expression of CD40, CD80 and CD83, and significantly increases the expression of the chemokine receptor CCR7. Conclusions: These experiments represent the first evidence for the functional importance of PKA anchoring in multiple aspects of DC biology.

Original languageEnglish (US)
Article numbere4807
JournalPLoS One
Volume4
Issue number3
DOIs
StatePublished - Mar 11 2009

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antigen presentation
Antigen Presentation
dendritic cells
Dendritic Cells
phosphotransferases (kinases)
Phosphotransferases
Antigens
cAMP-dependent protein kinase
Cyclic AMP-Dependent Protein Kinases
Cytology
cell biology
Cell Biology
peptides
antigens
Adenylate Kinase
AMP-activated protein kinase
CD4 Antigens
Peptides
T-cells
antigen-presenting cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Schillace, R. V., Miller, C. L., Pisenti, N., Grotzke, J. E., Swarbrick, G. M., Lewinsohn, D., & Carr, D. (2009). A-kinase anchoring in Dendritic cells is required for antigen presentation. PLoS One, 4(3), [e4807]. https://doi.org/10.1371/journal.pone.0004807

A-kinase anchoring in Dendritic cells is required for antigen presentation. / Schillace, Robynn V.; Miller, Casey L.; Pisenti, Neal; Grotzke, Jeff E.; Swarbrick, Gwendolyn M.; Lewinsohn, David; Carr, Daniel.

In: PLoS One, Vol. 4, No. 3, e4807, 11.03.2009.

Research output: Contribution to journalArticle

Schillace, RV, Miller, CL, Pisenti, N, Grotzke, JE, Swarbrick, GM, Lewinsohn, D & Carr, D 2009, 'A-kinase anchoring in Dendritic cells is required for antigen presentation', PLoS One, vol. 4, no. 3, e4807. https://doi.org/10.1371/journal.pone.0004807
Schillace RV, Miller CL, Pisenti N, Grotzke JE, Swarbrick GM, Lewinsohn D et al. A-kinase anchoring in Dendritic cells is required for antigen presentation. PLoS One. 2009 Mar 11;4(3). e4807. https://doi.org/10.1371/journal.pone.0004807
Schillace, Robynn V. ; Miller, Casey L. ; Pisenti, Neal ; Grotzke, Jeff E. ; Swarbrick, Gwendolyn M. ; Lewinsohn, David ; Carr, Daniel. / A-kinase anchoring in Dendritic cells is required for antigen presentation. In: PLoS One. 2009 ; Vol. 4, No. 3.
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