N-3 Polyunsaturated Fatty Acids Reduce Th17 Differentiation by Decreasing Responsiveness to Interleukin-6 in Mice
dc.contributor | Chapkin, Robert S | |
dc.creator | Allen, Marilyn Jean | |
dc.date.accessioned | 2016-08-01T05:30:14Z | |
dc.date.accessioned | 2017-04-07T20:10:26Z | |
dc.date.available | 2016-08-01T05:30:14Z | |
dc.date.available | 2017-04-07T20:10:26Z | |
dc.date.created | 2014-08 | |
dc.date.issued | 2014-05-29 | |
dc.description.abstract | CD4^(+) effector T cell subsets (e.g., Th1, Th17) are implicated in autoimmune and inflammatory disorders such as multiple sclerosis, psoriasis and rheumatoid arthritis. For optimal activation, IL-6 induces Th17 polarization and signals through the membrane-bound signal transducer, gp130. Previously, 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. Here we report that n-3 PUFA alter the response of CD4^(+) T cells to IL-6 in a lipid raft membrane-dependent fashion. Na?ve splenic CD4^(+) T cells from fat-1 mice exhibited significantly lower surface expression of the IL-6 receptor (IL-6R). This membrane bound receptor is known to be shed upon cellular activation in response to antigen; however, the release of soluble IL-6R after treatment with anti-CD3 and anti-CD28 was not changed in fat-1 mice suggesting that the decrease in surface expression is not due to ectodomain release. 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. | |
dc.identifier.uri | http://hdl.handle.net/1969.1/153215 | |
dc.language.iso | en | |
dc.subject | n-3 PUFA | |
dc.subject | lipid rafts | |
dc.subject | Th17 | |
dc.subject | IL-6-gp130-STAT3 | |
dc.title | N-3 Polyunsaturated Fatty Acids Reduce Th17 Differentiation by Decreasing Responsiveness to Interleukin-6 in Mice | |
dc.type | Thesis |