Details

Autor(en) / Beteiligte

• Rolph, Michael S
• Young, Timothy R
• Shum, Bennett O. V
• Gorgun, Cem Z
• Schmitz-Peiffer, Carsten
• Ramshaw, Ian A
• Hotamisligil, Gokhan S
• Mackay, Charles R

Titel

Regulation of Dendritic Cell Function and T Cell Priming by the Fatty Acid-Binding Protein aP2

Ist Teil von

• Journal of Immunology, 2006-12, Vol.177 (11), p.7794-7801

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2006

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• 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.