title: n3 PUFAs reduce mouse CD4+ T-cell ex vivo polarization into Th17 cells.
abstract: Little is known about the impact of n3 (ω3) PUFAs on polarization of CD4(+) T cells into effector subsets other than Th1 and Th2. We assessed the effects of dietary fat [corn oil (CO) vs. fish oil (FO)] and fermentable fiber [cellulose (C) vs. pectin (P)] (2 × 2 design) in male C57BL/6 mice fed CO-C, CO-P, FO-C, or FO-P diets for 3 wk on the ex vivo polarization of purified splenic CD4(+) T cells (using magnetic microbeads) into regulatory T cells [Tregs; forkhead box P3 (Foxp3(+)) cells] or Th17 cells [interleukin (IL)-17A(+) and retinoic acid receptor-related orphan receptor (ROR) γτ(+) cells] by flow cytometry. Treg polarization was unaffected by diet; however, FO independently reduced the percentage of both CD4(+) IL-17A(+) (P < 0.05) and CD4(+) RORγτ(+) cells (P < 0.05). Moreover, expression of another critical Th17-cell-related transcription factor, signal transducer and activator of transcription 3, was reduced by FO. Dietary FO reduced the surface expression of both IL-6R and IL-23R on polarized Th17 cells (P ≤ 0.05), thus interfering with the promotive effects of these critical cytokines on Th17 polarization. Additionally, C57BL/6 mice fed diets enriched in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or DHA + EPA similarly reduced Th17-cell polarization in comparison to CO by reducing expression of the Th17-cell signature cytokine (IL-17A; P = 0.0015) and transcription factor (RORγτ P = 0.02), whereas Treg polarization was unaffected. Collectively, these data show that n3 PUFAs exert a direct effect on the development of Th17 cells in healthy mice, implicating a novel n3 PUFA-dependent, anti-inflammatory mechanism of action via the suppression of the initial development of this inflammatory T-cell subset.
authors.affiliation: Program in Integrative Nutrition and Complex Diseases.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Monk
authors.forename: Tim Y
authors.initials: TY
authors.lastname: Hou
authors.forename: Harmony F
authors.initials: HF
authors.lastname: Turk
authors.forename: David N
authors.initials: DN
authors.lastname: McMurray
authors.forename: Robert S
authors.initials: RS
authors.lastname: Chapkin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003314:Corn Oil / Q000008:administration & dosage / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D020381:Interleukin-17; D003314:Corn Oil