Polyunsaturated Fatty Acids Block Dendritic Cell Activation and Function Independently of NF-κB Activation

Abstract

Polyunsaturated fatty acids (PUFAs) modulate immune responses leading to clinically significant beneficial effects in a variety of inflammatory disorders. PUFA effects on T cells have been extensively studied, but their influence on human dendritic cells (DCs), which are the most potent antigen-presenting cells and play a key role in initiating immune responses, has not been elucidated so far. Here we show that PUFAs of the n-3 and n-6 series (arachidonic and eicosapentaenoic acid) affect human monocyte-derived DC differentiation and inhibit their activation by LPS, resulting in altered DC surface molecule expression and diminished cytokine secretion. Furthermore, the potency to stimulate T cells was markedly inhibited in PUFA-treated DCs. The PUFA-mediated block in LPS-induced DC activation is reflected by diminished TNF-␣, IL-12p40, CD40, and COX-2 mRNA levels. Strikingly, typical LPS-induced signaling events such as degradation of IB and activation of NF-B were not affected by PUFAs, even though DC membrane lipid composition was markedly altered. Arachidonic and eicosapentaenoic acid both altered DC prostaglandin production, but inhibitors of cyclooxygenases and lipoxygenases did not abolish PUFA effects, indicating that the observed PUFA actions on DCs were independent of autoregulation via eicosanoids. These data demonstrate a unique interference with DC activation and function that could significantly contribute to the well known anti-inflammatory effects of PUFAs.

Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function

“…6 ) were not entirely in agreement with some in vitro studies showing that DHA suppressed LPS activation of macrophages and dendritic cells (43)(44)(45). This could be due to aforementioned differences (e.g., cell type, diet vs. in vitro treatment, etc.).…”

n-3 PUFA improves fatty acid composition, prevents palmitate-induced apoptosis, and differentially modifies B cell cytokine secretion in vitro and ex vivo

“…The rapid improvement in the n-6/n-3 ratio points to the possibility that n-3 PUFAs could be used as nutraceuticals to modify composition and organization to selectively initiate a change in cellular function with a high dose of PUFAs for a short time period. Based on data presented here and elsewhere, the most plausible splenic targets that respond to a change in membrane composition to suppress cellular function are CD4 + T cells and possibly DCs ( 13,15,37,38 ). The data from this study allow us to propose that n-3 PUFA inhibition of lymphocyte activation is not universal.…”

Thematic review series: The Immune System and Atherogenesis. The unusual suspects:an overview ofthe minor leukocyte populations in atherosclerosis

“…On the other hand, the maturation and antigen-presentation ability of dendritic cells can be inhibited by statins (80), the cholesterol-lowering class of drugs that has been found to have a number of immunomodulatory effects as well. Dendritic cells treated with polyunsaturated fatty acids of the n-3 and n-6 family also display a maturation block when challenged with lipopolysaccharide, suggesting that part of the reported anti-inflammatory and atheroprotective effect of these dietary fatty acids (81,82) may be linked to preventing dendritic cell activation (83). Finally, recent studies have identified other lipid mediators that may be responsible for retaining dendritic cells in the atherosclerotic plaque, namely PAF and 18:1 lysophosphatidic acid (84,85).…”