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

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.

Type Journal
ISBN 0022-1767 (Print)
Authors Rolph, M. S.;Young, T. R.;Shum, B. O.;Gorgun, C. Z.;Schmitz-Peiffer, C.;Ramshaw, I. A.;Hotamisligil, G. S.;Mackay, C. R. :
Publisher Name J IMMUNOL
Published Date 2006-01-01 00:00:00
Published Volume 177
Published Issue 11
Published Pages 7794-801
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17114450
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?2122_10608/06 Rolph 7794.pdf