Dietary Docosahexaenoic Acid Suppresses T Cell Protein Kinase Cθ Lipid Raft Recruitment and IL-2 Production

Yang, Fan; Ly, Lan H.; Barhoumi, Rola; McMurray, David N.; Chapkin, Robert S.

doi:10.4049/jimmunol.173.10.6151

Cited by 221 publications

(194 citation statements)

References 78 publications

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“…41 In this study, feeding FO did not significantly modify IL-2 production in MLN cells stimulated with a polyclonal T-cell mitogen (ConA), indicating that increasing dietary (n-3) PUFA does not suppress T-cell function in obese JCR:LA-cp rats, which has been reported in healthy animals. [42][43][44][45] Overall, our study is supportive of the concept that FO may be beneficial in skewed Th2 states, as observed in the gut-associated lymph tissue of obese JCR:LA-cp rats.…”

Section: Effects Of Feeding Fo On Mln Immune Cell Functionsupporting

confidence: 71%

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

2008

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Objective: Aberrant immune responses have been identified in obesity; however, immune cells of lymph nodes residing in the inflammatory environment of visceral adipose tissue have been largely overlooked. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce inflammation and modify T-cell function and therefore may improve immune function in obesity. Thus, we determined the effects of feeding fish oil (FO) containing EPA and DHA on mesenteric lymph node (MLN) immune cell function. Methods: In this study, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp) (n ¼ 10 per group) were randomized to one of three nutritionally adequate diets for 3 weeks: control (ctl, 0% EPA þ DHA), low FO (LFO, 0.8% w/w EPA þ DHA) or high FO (HFO, 1.4% w/w EPA þ DHA). Lean JCR:LA-cp (Cp/cp or Cp/Cp) rats (n ¼ 5) were fed ctl diet. MLN cell phospholipid (PL) fatty acid composition, phenotypes and cytokine production were measured. Results: Obese ctl rats produced more IL-1b, IL-4 and IL-10, despite a higher proportion of (nÀ3) polyunsaturated fatty acids (PUFAs) and a lower (nÀ6):(nÀ3) PUFA ratio in MLN PL compared with lean ctl rats (Po0.05). Concanavalin A-stimulated IL-2 production did not differ from lean rats even though obese ctl rats had a lower proportion of CD4 þ CD25 þ cells (Po0.05). Feeding FO to obese rats increased the incorporation of (nÀ3) PUFA into MLN PL and normalized production of IL-1b (HFO only), IL-4 and IL-10 to the levels similar to lean ctl rats (Po0.05). Conclusion: We demonstrate for the first time that obese JCR:LA-cp rats have impaired responses of MLN immune cells to mitogen stimulation and altered PL fatty acid composition. Feeding FO lowered the ex vivo inflammatory response (HFO only) and production of Th2 cytokines, without changing IL-2 production from ConA-stimulated splenocytes, which may occur independent of leptin signalling.

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Section: Effects Of Feeding Fo On Mln Immune Cell Functionsupporting

confidence: 71%

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

2008

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“…showed that PUFA treatment alters T cell membrane lipid composition in vitro and in vivo (21,27,28) causing functional defects in T cell signaling (29,30). Hence, we investigated whether also DCs incorporate exogenous PUFAs into cell membranes leading to altered membrane lipid composition.…”

Section: Pufa Treatment Leads To Altered Membrane Lipid Composition Omentioning

confidence: 99%

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

Zeyda

Säemann

Stuhlmeier³

et al. 2005

Journal of Biological Chemistry

123

108

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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.

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“…Based on the evidence from cell-culture and animal-feeding studies it has been shown that n-3 PUFA supplementation modifies raft formation in T cells, which in turn impairs the signalling mechanism of these cells (107,108) . Thus, the exposure of T cells to n-3 fatty acid supplementation can alter the chemical structure of rafts which can consequently affect their function (109,110) .…”

Section: Epa-derived Eicosanoids Produced Via Cyclo-oxygenase and Lipmentioning

confidence: 99%

n-3 Fatty acids and asthma

2016

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Asthma is one of the most common and prevalent problems worldwide affecting over 300 million individuals. There is some evidence from observational and intervention studies to suggest a beneficial effect of n-3 PUFA in inflammatory diseases, specifically asthma. Marine-based n-3 PUFA have therefore been proposed as a possible complementary/alternative therapy for asthma. The proposed anti-inflammatory effects of n-3 fatty acids may be linked to a change in cell membrane composition. This altered membrane composition following n-3 fatty acid supplementation (primarily EPA and DHA) can modify lipid mediator generation via the production of eicosanoids with a reduced inflammatory potential/impact. A recently identified group of lipid mediators derived from EPA including E-series resolvins are proposed to be important in the resolution of inflammation. Reduced inflammation attenuates the severity of asthma including symptoms (dyspnoea) and exerts a bronchodilatory effect. There have been no major health side effects reported with the dietary supplementation of n-3 fatty acids or their mediators; consequently supplementing with n-3 fatty acids is an attractive non-pharmacological intervention which may benefit asthma.

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Dietary Docosahexaenoic Acid Suppresses T Cell Protein Kinase Cθ Lipid Raft Recruitment and IL-2 Production

Cited by 221 publications

References 78 publications

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

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

n-3 Fatty acids and asthma

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