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n‐3 Polyunsaturated fatty acids reduce Th17 polarization by decreasing responsiveness to interleukin‐6 (382.3)
Author(s) -
Allen M. Jeannie,
Fan YangYi,
Monk Jennifer,
Hou Tim,
Barhoumi Rola,
McMurray David,
Chapkin Robert
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.382.3
Subject(s) - lipid raft , t cell , chemistry , cytokine , microbiology and biotechnology , polyunsaturated fatty acid , stat3 , glycoprotein 130 , endocrinology , medicine , immunology , biology , signal transduction , biochemistry , immune system , fatty acid
CD4 + effector T cell subsets (e.g., Th1, Th17) are implicated in autoimmune and inflammatory disorders such as multiple sclerosis, psoriasis and rheumatoid arthritis. We have demonstrated that n‐3 polyunsaturated fatty acids (PUFA), when supplied in the diet or in fat‐1 transgenic mice which generate n‐3 PUFA de novo, suppress CD4 + T cell activation and differentiation into pathogenic Th17 cells. We hypothesized that n‐3 PUFA alter the response of CD4 + T cells to IL‐6 in a lipid raft membrane‐dependent fashion. IL‐6 induces Th17 polarization and signals through the membrane‐bound signal transducer, gp130. Upon activation, naïve splenic CD4 + T cells from fat‐1 mice exhibited significantly lower surface expression of the IL‐6 Receptor (IL‐6R). However, the release of soluble IL‐6R was unaffected by treatment. We observed a significant 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 STAT3, a downstream target of IL‐6‐dependent signaling, was also decreased in response to exogenous IL‐6 in fat‐1 CD4 + T cells. Our results suggest that n‐3 PUFA suppress Th17 cell differentiation, in part, by reducing membrane raft‐dependent responsiveness to IL‐6, an essential polarizing cytokine. Grant Funding Source : Supported by the NIH and USDA‐Vegetable Crop Improvement Center