Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

Yessoufou, Akadiri; Plé, Aude; Moutaïrou, Kabirou; Hichami, Aziz; Khan, Naim Akhtar

doi:10.1194/jlr.m900101-jlr200

Cited by 86 publications

(77 citation statements)

References 49 publications

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“…5A). This observation is consistent with previous studies showing decreased Lselectin expression in response to DHA (46). Because L-selectin is important in lymphocyte migration to the mesenteric lymph nodes and Peyer's patches (37), our data suggest that DFO may decrease the ability of Treg cells to migrate to lymph nodes in close proximity to the site of infection.…”

Section: Discussionsupporting

confidence: 82%

“…+ CD25 + populations in the mesenteric lymph nodes, FoxP3 mean fluorescence intensity expression was enhanced in both the spleen and mesenteric lymph nodes in DFO-fed mice (Table 2). Indeed, a recent study by Yessoufou and colleagues (46) showed that dietary DHA increases FoxP3 expression in murine Treg cells possibly through inhibition of SMAD7. The authors also noted that upregulation of FoxP3 did not necessarily correlate with the suppressive capacity of Treg cells because Treg cells from DHA-fed animals failed to suppress the proliferation of cocultured CD4 + T effector cells also derived from DHA-fed animals.…”

Section: Discussionmentioning

confidence: 99%

“…In general, it seems that FO supplementation may generate a depressed immune environment through alterations in cytokine production, T-cell proliferation, and T-cell-mediated cytotoxicity (23). DHA can exclusively suppress T regulatory (Treg) function (29). Interestingly, the immunomodulatory effects of DHA +EPA may be beneficial under certain circumstances such as chronic inflammation, but could be deleterious in acute pro-inflammatory and immune responses to cancer.…”

Section: Introductionmentioning

confidence: 99%

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Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

et al. 2010

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Inflammatory bowel diseases (IBD) increase the risk of developing colorectal cancer. Dietary components that reduce inflammation are associated with lower cancer risk. The long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is present in fish oil and has potent anti-inflammatory properties. The objective of this study is to determine whether dietary fish oil enriched with DHA (DFO) could reduce experimentally induced colitis and colon cancer risk in a mouse model. When SMAD3−/− mice are exposed to Helicobacter hepaticus, mild colitis is observed 4 weeks postinfection. Mice were fed isocaloric diets modified to include corn oil, safflower oil, or DFO (doses ranging from 0.75% to 6.00%) as the fatty acid source for 8 weeks. Mice were gavaged with H. hepaticus; DFO feeding was continued; and mice were sacrificed 4 weeks after infection. The colon and cecum were collected for histopathology. Spleens and mesenteric lymph nodes were collected and analyzed for T-cell populations using flow cytometry. Contrary to expectations, DFO induced severe colitis and adenocarcinoma formation. DFO consumption was associated with decreased CD8 + cell frequency and diminished CD69 expression on CD4 + and CD8 + T-cell populations. Mice consuming DFO also exhibited higher FoxP3 + CD25 + CD4 + T regulatory cell frequency, FoxP3 expression, and altered L-selectin expression during infection. We concluded that DFO-fed mice may be less equipped to mount a successful response to H. hepaticus infection, increasing colon cancer risk. These results support the need to establish a tolerable upper limit for DHA intake particularly in the context of chronic inflammatory conditions such as IBD.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

et al. 2010

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“…The insulin-mediated suppression of IL-10 production was dependent on AKT and mTOR, but not the MEK/ ERK signaling pathway, which is also activated by insulin (30). Of the few studies that have investigated the relationship between AKT signaling and IL-10 production in Tregs, some have reported an inverse association between AKT activation and IL-10 production in Tregs (38, 39) much like our data, whereas other studies suggest the opposite (40)(41)(42). Thus, the role of AKT signaling in IL-10 production by Tregs may be context dependent.…”

Section: Discussionsupporting

confidence: 77%

Insulin Inhibits IL-10–Mediated Regulatory T Cell Function: Implications for Obesity

Han

Patterson

Speck

et al. 2014

The Journal of Immunology

139

134

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Chronic inflammation is known to promote metabolic dysregulation in obesity and type 2 diabetes. Although the precise origin of the unchecked inflammatory response in obesity is unclear, it is known that overproduction of proinflammatory cytokines by innate immune cells affects metabolism. For example, TNF-α contributes to the inability of cells to respond to insulin and to the increase in levels of insulin. Whether this hyperinsulinemia itself is part of a feedback loop that affects the progression of chronic adipose inflammation is unknown. In this article, we show that regulatory T cells (Tregs) express the insulin receptor, and that high levels of insulin impair the ability of Tregs to suppress inflammatory responses via effects on the AKT/mTOR signaling pathway. Insulin activated AKT signaling in Tregs, leading to inhibition of both IL-10 production and the ability of Tregs to suppress the production of TNF-α by macrophages in a contact-independent manner. The effect of insulin on Treg suppression was limited to IL-10 production and it did not alter the expression of other proteins associated with Treg function, including CTLA-4, CD39, and TGF-β. In a model of diet-induced obesity, Tregs from the visceral adipose tissue of hyperinsulinemic, obese mice showed a similar specific decrease in IL-10 production, as well as a parallel increase in production of IFN-γ. These data suggest that hyperinsulinemia may contribute to the development of obesity-associated inflammation via a previously unknown effect of insulin on the IL-10–mediated function of Tregs.

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“…Recentemente, efeitos imunomodulatórios do EPA (AGI n-3) foram relatados por induzir a ativação de células Treg via mecanismo dependente de receptores nucleares, atuando como imunossupressor (Iwami et al, 2011), enquanto DHA (AGI n-3) reduziu as funções imunossupressoras e migratórias dessas células (Yessoufou et al, 2009).…”

Section: Agi Exercem Efeitos Imunomoduladores Sobre As Funções Dos LIunclassified

Cellular and molecular biomarkers involved in immune-inflammatory response modulated by unsaturated fatty acids

Oliveira

Nunes-Pinheiro

2013

AVB

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RESUMO -A resposta imunológica é um processo complexo que envolve a interação e sinalização de diferentes tipos celulares e moleculares, conhecidos como biomarcadores, os quais atuam de modo coordenado para promover a defesa do organismo. Essa resposta inicia-se com a instalação do processo inflamatório, que culmina com eliminação de agentes microbianos e cicatrização do tecido afetado, podendo evoluir para uma resposta mais específica. Muitos mediadores produzidos durante essas reações, sobretudo aqueles de natureza lipídica e peptídica, podem ser originados da imunomodulação promovida por ácidos graxos insaturados fornecidos pela dieta ou sintetizados endogenamente. Ácidos graxos insaturados são constituintes das membranas celulares e reguladores da expressão gênica, atuando nas vias de sinalização, transdução de sinais e proliferação celular e gerando produtos que regulam os mecanismos da imunidade humoral e celular. Esses lipídios apresentam várias propriedades biológicas, incluindo importantes efeitos imunomoduladores sobre a inflamação e a cicatrização. Ácidos graxos insaturados regulam a ativação de diversas células envolvidas nesses processos, tais como macrófagos, neutrófilos, linfócitos, queratinócitos e células dendríticas, bem como a secreção de seus produtos, exercem efeitos sobre enzimas e fatores de transcrição gênica, estimulando ou inibindo a produção de eicosanóides, como as prostaglandinas e leucotrienos, citocinas, moléculas de adesão, fatores de crescimento e outras moléculas específicas envolvidas nas diferentes fases do reparo tecidual, além de modular o estresse oxidativo. Neste contexto, esse artigo tem como objetivo revisar o papel dos principais biomarcadores celulares e moleculares envolvidos na resposta imune-inflamatória modulada por ácidos graxos insaturados.Palavras-Chave: Ômega-3, ômega-6, ômega-9, inflamação, cicatrização, imunomodulação.ABSTRACT -Immune response is a complex process that involves interaction and signaling of different cell and molecular types, known as biomarkers, which are organized to promote the defense of organism. This response begins with installation of the inflammatory process and culminates with elimination of the microbial agents, damage tissue and repair. The inflammatory response can progress to a more specific process. Many mediators are produced during inflammation, especially lipid and peptide mediators. These substances can be generated from immunomodulation promoted by unsaturated fatty acids provided by dietary or endogenously synthesized. Unsaturated fatty acids are constituents of cell membranes and regulators of gene expression and act on signaling pathways, signal transduction and cell proliferation, generating products that regulate the mechanisms of humoral and cellular immunity. These lipids have multiple biological properties, including important immunomodulatory effects on inflammation and wound healing. Unsaturated fatty acids regulate the activation of various cells involved in these processes, such as macrophages, neutrophils, lymp...

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Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

Cited by 86 publications

References 49 publications

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

Dietary Fish Oil Alters T Lymphocyte Cell Populations and Exacerbates Disease in a Mouse Model of Inflammatory Colitis

Insulin Inhibits IL-10–Mediated Regulatory T Cell Function: Implications for Obesity

Cellular and molecular biomarkers involved in immune-inflammatory response modulated by unsaturated fatty acids

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