| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,
,
* Immunology and Inflammation Research Program, Garvan Institute for Medical Research, Darlinghurst, New South Wales, Australia;
Cooperative Research Centre for Asthma, Camperdown, New South Wales, Australia;
St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, Australia;
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115;
¶ Diabetes and Obesity Research Program, Garvan Institute for Medical Research, Darlinghurst, New South Wales, Australia; and
|| Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, Australia
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 I
B
was also impaired in aP2-deficient DCs, indicative of reduced signaling through the IB kinase-NF-B 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-
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- 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported in part by grants from National Health and Medical Research Council and Cooperative Research Centre for Asthma (to M.S.R. and C.R.M.), the National Institutes of Health (DK064360 and HL65405), and the Sandler Program (to G.S.H.).
2 Address correspondence and reprint requests to Dr. Michael S. Rolph, Immunology and Inflammation Research Program, Garvan Institute for Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia. E-mail address: m.rolph{at}garvan.org.au
3 Abbreviations used in this paper: DC, dendritic cell; FABP, fatty acid-binding protein; PPAR, peroxisome proliferator-activated receptor; IKK, IB kinase; rm, recombinant murine; BMDC, bone marrow-derived DC; EV, ectromelia virus; WT, wild type; imDC, immature DC; KLH, keyhole limpet hemocyanin.
This article has been cited by other articles:
|
|
 |
|
  J. M. Reynolds, Q. Liu, K. C. Brittingham, Y. Liu, M. Gruenthal, C. Z. Gorgun, G. S. Hotamisligil, R. D. Stout, and J. Suttles Deficiency of Fatty Acid-Binding Proteins in Mice Confers Protection from Development of Experimental Autoimmune Encephalomyelitis J. Immunol., July 1, 2007; 179(1): 313 - 321. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
