n–3 PUFAs Reduce T-Helper 17 Cell Differentiation by Decreasing Responsiveness to Interleukin-6 in Isolated Mouse Splenic CD4+ T Cells  

Oleh:

Allen, M. Jeannie ; Yang-Yi, Fan ; Monk, Jennifer M. ; Tim, Y. Hou ; Barhoumi, Rola

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 144 no. 08 (Aug. 2014), page 1306-1313.

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Perpustakaan FK Nomor Panggil: J42.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

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Isi artikel

Cluster of differentiation 4+ (CD4+) effector T-cell subsets [e.g., T-helper (Th) 1 and Th17] are implicated in autoimmune and inflammatory disorders such as multiple sclerosis, psoriasis, and rheumatoid arthritis. Interleukin (IL)-6 is a pleiotropic cytokine that induces Th17 polarization via signaling through the membrane-bound transducer glycoprotein 130 (GP130). Previously, we demonstrated that n–3 (?-3) polyunsaturated fatty acids (PUFAs) reduce CD4+ T-cell activation and differentiation into pathogenic Th17 cells by 25–30%. Here we report that n–3 PUFAs alter the response of CD4+ T cells to IL-6 in a lipid raft membrane–dependent manner. Naive splenic CD4+ T cells from fat-1 transgenic mice exhibited 30% lower surface expression of the IL-6 receptor. This membrane-bound receptor is known to be shed during cellular activation, but the release of soluble IL-6 receptor after treatment with anti-CD3 and anti-CD28 was not changed in the CD4+ T cells from fat-1 mice, suggesting that the decrease in surface expression was not due to ectodomain release. We observed a significant 20% decrease in the association of GP130 with lipid rafts in activated fat-1 CD4+ T cells and a 35% reduction in GP130 homodimerization, an obligate requirement for downstream signaling. The phosphorylation of signal transducer and activator of transcription 3 (STAT3), a downstream target of IL-6–dependent signaling, was also decreased by 30% in response to exogenous IL-6 in fat-1 CD4+ T cells. Our results suggest that n–3 PUFAs suppress Th17 cell differentiation in part by reducing membrane raft–dependent responsiveness to IL-6, an essential polarizing cytokine.

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