Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2

Michael Rolph, Timothy Young, Bennett Shum, Cem Z. Gorgun, Carsten Schmitz-Peiffer, Ian Ramshaw, Gakhan S. Hotamisligil, Charles Mackay

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The fatty acid-binding protein (FABP) family consists of a number of conserved cytoplasmic proteins with roles in intracellular lipid transport, storage, and metabolism. Examination of a comprehensive leukocyte gene expression database revealed strong expression of the adipocyte FABP aP2 in human monocyte-derived dendritic cells (DCs). We isolated bone marrow-derived DC from aP2-deficient mice, and showed that expression of DC cytokines including IL-12 and TNF was significantly impaired in these cells. Degradation of IkappaBalpha was also impaired in aP2-deficient DCs, indicative of reduced signaling through the IkappaB kinase-NF-kappaB pathway. The cytokine defect was selective because there was no effect on Ag uptake or expression of MHC class II, CD40, CD80, or CD86. In an MLR, aP2-deficient DCs stimulated markedly lower T cell proliferation and cytokine production than did wild-type DCs. Moreover, aP2-deficient mice immunized with keyhole limpet hemocyanin/CFA showed reduced production of IFN-gamma by restimulated draining lymph node cells, suggesting a similar defect in DC function in vivo. Similarly, infection of aP2-deficient mice with the natural mouse pathogen ectromelia virus resulted in substantially lower production of IFN-gamma by CD8+ T cells. Thus, FABP aP2 plays an important role in DC function and T cell priming, and provides an additional link between metabolic processes and the regulation of immune responses
Original languageEnglish
Pages (from-to)7794-7801
Number of pages8
JournalJournal of Immunology
Volume177
Issue number11
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint Dive into the research topics of 'Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2'. Together they form a unique fingerprint.

  • Cite this

    Rolph, M., Young, T., Shum, B., Gorgun, C. Z., Schmitz-Peiffer, C., Ramshaw, I., Hotamisligil, G. S., & Mackay, C. (2006). Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2. Journal of Immunology, 177(11), 7794-7801. https://doi.org/10.4049/jimmunol.177.11.7794