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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

Journal article
Authors Johan Carlsson
Agnes E Wold
Ann-Sofie Sandberg
Sofia M Östman
Published in PLoS ONE
Volume 10
Issue 11
Pages e0143741
ISSN 1932-6203
Publication year 2015
Published at Institute of Biomedicine, Department of Infectious Medicine
Pages e0143741
Language en
Links dx.doi.org/10.1371/journal.pone.014...
https://gup.ub.gu.se/file/177149
Keywords Polyunsaturated fatty acid; Arachidonic acid; Docosahexaenoic Acid; DHA; omega 3; In vitro; Omega 6; Mouse; Immune regulation; Dendritic cell; T cell
Subject categories Molecular biology, Cell Biology, Cell biology, Immunology in the medical area, Immunobiology

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 naive T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 muM fatty acids; alpha-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 Violetlow) 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 IFNgamma. 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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