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

48 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

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Dendritic Cells
Fatty Acids
T-Lymphocytes
Proteins
Fatty Acid-Binding Proteins
Cytokines
Ectromelia virus
I-kappa B Kinase
NF-kappa B
Interleukin-12
Adipocytes
Monocytes
Leukocytes
Lymph Nodes
Bone Marrow
Cell Proliferation
Databases
Lipids
Gene Expression
Infection

Cite this

Rolph, M., Young, T., Shum, B., Gorgun, C. Z., Schmitz-Peiffer, C., Ramshaw, I., ... 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
Rolph, Michael ; Young, Timothy ; Shum, Bennett ; Gorgun, Cem Z. ; Schmitz-Peiffer, Carsten ; Ramshaw, Ian ; Hotamisligil, Gakhan S. ; Mackay, Charles. / Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2. In: Journal of Immunology. 2006 ; Vol. 177, No. 11. pp. 7794-7801.
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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",
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Rolph, M, Young, T, Shum, B, Gorgun, CZ, Schmitz-Peiffer, C, Ramshaw, I, Hotamisligil, GS & Mackay, C 2006, 'Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2', Journal of Immunology, vol. 177, no. 11, pp. 7794-7801. https://doi.org/10.4049/jimmunol.177.11.7794

Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2. / Rolph, Michael; Young, Timothy; Shum, Bennett; Gorgun, Cem Z.; Schmitz-Peiffer, Carsten; Ramshaw, Ian; Hotamisligil, Gakhan S.; Mackay, Charles.

In: Journal of Immunology, Vol. 177, No. 11, 2006, p. 7794-7801.

Research output: Contribution to journalArticle

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T1 - Regulation of dendritic cell function and T cell priming by the fatty acid-bonding protein AP2

AU - Rolph, Michael

AU - Young, Timothy

AU - Shum, Bennett

AU - Gorgun, Cem Z.

AU - Schmitz-Peiffer, Carsten

AU - Ramshaw, Ian

AU - Hotamisligil, Gakhan S.

AU - Mackay, Charles

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N2 - 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

AB - 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

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DO - 10.4049/jimmunol.177.11.7794

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EP - 7801

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JF - Journal of Immunology

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