Contributions
Abstract: P488
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors
Background: Growing evidence suggests that ingredients of a 'Western diet' like high intake of sodium chloride (NaCl) and long-chain saturated fatty acids (LCFA) may impact immune responses in multiple sclerosis (MS). Recently, we have shown that high dietary salt as well as LCFA, like lauric acid (LA), aggravate T helper (Th) 17 cell responses and the course of experimental autoimmune encephalomyelitis (EAE). However, there is still little understanding on the mechanisms linking environmental factors to disease pathogenesis, genetic predisposition, and the immune system in MS. Here, we investigate synergistic effects of combining increased NaCl concentrations and LA on CD4+ T cell populations in neuroinflammation.
Methods: Naïve CD4+ T cells were treated with an excess of 40 mM NaCl and/or 250 µM LA in vitro to investigate Th cell differentiation, cytokine secretion and gene expression. We employed ex vivo analyses of murine myelin oligodendrocyte glycoprotein induced EAE to investigate effects of a combined salt and LCFA challenge on disease severity and T cell subsets in vivo.
Results: The combined challenge of LA with NaCl enhanced the differentiation of Th1 (30.2% ctrl vs. 46.9% NaCl+LA) and Th17 cells (1% ctrl vs. 4.5% NaCl+LA) as well as pro-inflammatory cytokine and gene expression compared to controls in vitro (n=4-5; p< 0.05). For Th17 cells, an additive effect of LA and NaCl was observed in differentiation assays (4.5% NaCl+LA vs. 2.5% NaCl resp. 2.7% LA, n=5, p< 0.01) and on IL-17, GM-CSF and IL-2 gene expression (n=4; p< 0.05). In EAE, the combination of a NaCl- and LA-rich diet aggravated the disease course (score 2.4±0.7 ctrl vs. 3.4±-0.6 NaCl vs. 3.7±0.6 NaCl+LA, n=15-20 per group, p< 0.01) and increased T cell infiltration into the central nervous system (CNS) by around one third (n=9-13, p< 0.05).
Conclusions: Our findings demonstrate additive effects of NaCl and LA on Th cell polarization and pro-inflammatory cytokine expression in vitro. In the EAE model, a NaCl- and LA-rich diet exacerbated disease course and Th cell responses. These data further underline the relevance of a 'Western diet' as risk factor for MS.
Disclosure:
Anna Hammer: nothing to disclose
Anne Schliep: nothing to disclose
Stefanie Jörg: nothing to disclose
Dominik N. Müller: nothing to disclose
Ralf A. Linker received compensation for activities with or research support from Allmirall, Bayer Health Care, Biogen, Fresenius, Genzyme, Merck, Novartis Pharma, Roche, TEVA.
Markus Kleinewietfeld received compensation for activities with TEVA.
Aiden Haghikia received compensation for activities with or research support from Bayer Health Care, Biogen, Fresenius, Novartis Pharma, TEVA.
Ralf Gold received compensation for activities with or research support from Bayer Health Care, Biogen, Genzyme, Merck, Novartis Pharma, TEVA.
Abstract: P488
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 17 Environmental factors
Background: Growing evidence suggests that ingredients of a 'Western diet' like high intake of sodium chloride (NaCl) and long-chain saturated fatty acids (LCFA) may impact immune responses in multiple sclerosis (MS). Recently, we have shown that high dietary salt as well as LCFA, like lauric acid (LA), aggravate T helper (Th) 17 cell responses and the course of experimental autoimmune encephalomyelitis (EAE). However, there is still little understanding on the mechanisms linking environmental factors to disease pathogenesis, genetic predisposition, and the immune system in MS. Here, we investigate synergistic effects of combining increased NaCl concentrations and LA on CD4+ T cell populations in neuroinflammation.
Methods: Naïve CD4+ T cells were treated with an excess of 40 mM NaCl and/or 250 µM LA in vitro to investigate Th cell differentiation, cytokine secretion and gene expression. We employed ex vivo analyses of murine myelin oligodendrocyte glycoprotein induced EAE to investigate effects of a combined salt and LCFA challenge on disease severity and T cell subsets in vivo.
Results: The combined challenge of LA with NaCl enhanced the differentiation of Th1 (30.2% ctrl vs. 46.9% NaCl+LA) and Th17 cells (1% ctrl vs. 4.5% NaCl+LA) as well as pro-inflammatory cytokine and gene expression compared to controls in vitro (n=4-5; p< 0.05). For Th17 cells, an additive effect of LA and NaCl was observed in differentiation assays (4.5% NaCl+LA vs. 2.5% NaCl resp. 2.7% LA, n=5, p< 0.01) and on IL-17, GM-CSF and IL-2 gene expression (n=4; p< 0.05). In EAE, the combination of a NaCl- and LA-rich diet aggravated the disease course (score 2.4±0.7 ctrl vs. 3.4±-0.6 NaCl vs. 3.7±0.6 NaCl+LA, n=15-20 per group, p< 0.01) and increased T cell infiltration into the central nervous system (CNS) by around one third (n=9-13, p< 0.05).
Conclusions: Our findings demonstrate additive effects of NaCl and LA on Th cell polarization and pro-inflammatory cytokine expression in vitro. In the EAE model, a NaCl- and LA-rich diet exacerbated disease course and Th cell responses. These data further underline the relevance of a 'Western diet' as risk factor for MS.
Disclosure:
Anna Hammer: nothing to disclose
Anne Schliep: nothing to disclose
Stefanie Jörg: nothing to disclose
Dominik N. Müller: nothing to disclose
Ralf A. Linker received compensation for activities with or research support from Allmirall, Bayer Health Care, Biogen, Fresenius, Genzyme, Merck, Novartis Pharma, Roche, TEVA.
Markus Kleinewietfeld received compensation for activities with TEVA.
Aiden Haghikia received compensation for activities with or research support from Bayer Health Care, Biogen, Fresenius, Novartis Pharma, TEVA.
Ralf Gold received compensation for activities with or research support from Bayer Health Care, Biogen, Genzyme, Merck, Novartis Pharma, TEVA.