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

J Immunol. 2006 Dec 1;177(11):7794-801. doi: 10.4049/jimmunol.177.11.7794.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Fatty Acid-Binding Proteins / immunology*
  • Fatty Acid-Binding Proteins / metabolism
  • Gene Expression
  • I-kappa B Proteins / metabolism
  • Interleukin-12 / metabolism
  • Lymphocyte Activation / immunology*
  • Lymphocyte Culture Test, Mixed
  • Mice
  • NF-KappaB Inhibitor alpha
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Fatty Acid-Binding Proteins
  • I-kappa B Proteins
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Interleukin-12