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The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro.

Carlsson JA, Wold AE, Sandberg AS, Östman SM - PLoS ONE (2015)

Bottom Line: Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells.Fatty acids were taken up by the DCs, as shown by gas chromatography analysis.However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+).

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.

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Cytokines in co-culture supernatant.Levels of (A) IL-10 and (B) IFNγ in DC: T cell co-culture supernatants. T cells were co-cultured for 6 days with dendritic cells (DCs) previously supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol only (Ctrl). Each dot represents one individual. Horizontal black solid lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of two independent experiments. p-values: * <0.05, ** <0.01, *** <0.001, **** <0.0001.
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pone.0143741.g010: Cytokines in co-culture supernatant.Levels of (A) IL-10 and (B) IFNγ in DC: T cell co-culture supernatants. T cells were co-cultured for 6 days with dendritic cells (DCs) previously supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol only (Ctrl). Each dot represents one individual. Horizontal black solid lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of two independent experiments. p-values: * <0.05, ** <0.01, *** <0.001, **** <0.0001.

Mentions: The DC: T cell co-culture supernatant from samples with arachidonic acid-primed DCs contained lower levels of IL-10 and IFNγ compared to control (Fig 10A and 10B), which supports the low T-cell stimulatory activity with arachidonic acid. No reduction of cytokines was shown with DHA-primed DCs, compared to controls, which suggests less T-cell suppression (Fig 10A and 10B). IL-12 p70 was below limit of detection, TGF-β1 was in pair with the levels in fresh complete IMDM, with no differences between the groups, while sCD83 was found in higher levels than those found in DC culture supernatant, but still without differences between the groups (S7 Fig).


The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro.

Carlsson JA, Wold AE, Sandberg AS, Östman SM - PLoS ONE (2015)

Cytokines in co-culture supernatant.Levels of (A) IL-10 and (B) IFNγ in DC: T cell co-culture supernatants. T cells were co-cultured for 6 days with dendritic cells (DCs) previously supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol only (Ctrl). Each dot represents one individual. Horizontal black solid lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of two independent experiments. p-values: * <0.05, ** <0.01, *** <0.001, **** <0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664484&req=5

pone.0143741.g010: Cytokines in co-culture supernatant.Levels of (A) IL-10 and (B) IFNγ in DC: T cell co-culture supernatants. T cells were co-cultured for 6 days with dendritic cells (DCs) previously supplemented with fatty acids (50 μM); arachidonic acid (AA), docosahexaenoic acid (DHA), oleic acid (OA) or ethanol only (Ctrl). Each dot represents one individual. Horizontal black solid lines show median value. The median from the control group has been extended with a dotted line for easy comparison to the other groups. Statistical mean difference was compared to the control group. Data are representative of two independent experiments. p-values: * <0.05, ** <0.01, *** <0.001, **** <0.0001.
Mentions: The DC: T cell co-culture supernatant from samples with arachidonic acid-primed DCs contained lower levels of IL-10 and IFNγ compared to control (Fig 10A and 10B), which supports the low T-cell stimulatory activity with arachidonic acid. No reduction of cytokines was shown with DHA-primed DCs, compared to controls, which suggests less T-cell suppression (Fig 10A and 10B). IL-12 p70 was below limit of detection, TGF-β1 was in pair with the levels in fresh complete IMDM, with no differences between the groups, while sCD83 was found in higher levels than those found in DC culture supernatant, but still without differences between the groups (S7 Fig).

Bottom Line: Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells.Fatty acids were taken up by the DCs, as shown by gas chromatography analysis.However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+).

View Article: PubMed Central - PubMed

Affiliation: Department of Infectious Diseases, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

ABSTRACT
Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violet low) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells.

Show MeSH
Related in: MedlinePlus