The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy

Ni, Fen-Fen; Li, Chengrong; Liao, Jianxiang; Wang, Guobing; Lin, Sufang; Xia, Yu; Wen, Jialun

doi:10.1016/j.seizure.2016.03.006

Cited by 43 publications

(29 citation statements)

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“…Interestingly, up-regulated serum levels of IL-17 were reduced after ketogenic diet, which partially controlled seizures in some pediatric patients with intractable epilepsy. A concomitant increase of circulating T reg cells in the blood was noted in these patients, suggesting a balance between Th17 and T reg cell cells in the regulation of seizure ( Ni et al, 2016 ). To our knowledge, there have been no studies that provide an association of GM-CSF with epilepsy.…”

Section: Discussionmentioning

confidence: 99%

Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy

Robinson

Ishii

et al. 2018

Journal of Experimental Medicine

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Section: Discussionmentioning

confidence: 99%

Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy

Robinson

Ishii

et al. 2018

Journal of Experimental Medicine

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“…Interestingly PGE2 exerts anti-inflammatory properties by EP4 receptor-mediated action [ 71 ]. Moreover, a Th17/T reg imbalance is characteristic of childhood intractable epilepsy and was corrected by ketogenic diet [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

2018

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BackgroundAdapted ketogenic diet (AKD) and caloric restriction (CR) have been suggested as alternative therapeutic strategies for inflammatory, hyperproliferative and neurodegenerative diseases. Pro-inflammatory eicosanoids have been implicated in the pathogenesis of multiple sclerosis since they augment vascular permeability and induce leukocyte migration into the brain. We explored the impact of ketogenic diets on gene expression of biosynthetic enzymes for pro- (ALOX5, COX1, COX2) and anti-inflammatory (ALOX15) eicosanoids in patients with relapsing-remitting multiple sclerosis.Methods60 adults were prospectively recruited for this six months randomized controlled trial and the impact of dietary treatment on the Multiple Sclerosis Quality of Life-54 index (ClinicalTrials.gov (NCT01538355) has previously been published. Here we explored 24 patients (8 controls, 5 on CR and 11 on AKD). For statistical analysis we combined the two diet groups to a single pooled treatment group.FindingsInter-group comparison indicated that expression of the pro-inflammatory ALOX5 in the pooled treatment group was significantly (p < 0.05) reduced when compared with the control group. Moreover, intra-group comparison (same individuals before and after dietary treatment) suggested significantly impaired expression of other pro-inflammatory enzymes, such as COX1 (p < 0.001) and COX2 (p < 0.05). Finally, pretreatment cross-group analysis revealed a significant positive correlation between expression of pro-inflammatory ALOX5 and COX2 and an inverse correlation of ALOX5 and COX1 expression with the MSQoL-54 index.InterpretationKetogenic diets can reduce the expression of enzymes involved in the biosynthesis of pro-inflammatory eicosanoids. Pharmacological interference with eicosanoid biosynthesis might constitute a strategy supplementing current therapeutic approaches for MS.

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Background: B-and T-lymphocyte attenuator (BTLA/CD272) is a coreceptor constitutively expressed on B cells [1,2]. Upon B cell activation via the B cell receptor (BCR), BTLA co-localizes with Src homology region 2 domain-containing phosphatase-1 (SHP-1) and thus negatively regulates BCR signaling [2].

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confidence: 99%

“…Upon B cell activation via the B cell receptor (BCR), BTLA co-localizes with Src homology region 2 domain-containing phosphatase-1 (SHP-1) and thus negatively regulates BCR signaling [2]. A recent study found that CD4+ T cells from SLE patients fail to upregulate BTLA upon activation [3], however, data on BTLA expression and function for B cells in autoimmunity is missing.…”

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confidence: 99%

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Ab0194 btla Expression Is Reduced on Sle B Cell Subsets

Wiedemann

Stefanski

Lino

et al. 2019

Abstracts Accepted for Publication

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BackgroundB- and T-lymphocyte attenuator (BTLA/CD272) is a co-receptor constitutively expressed on B cells [1, 2]. Upon B cell activation via the B cell receptor (BCR), BTLA co-localizes with Src homology region 2 domain-containing phosphatase-1 (SHP-1) and thus negatively regulates BCR signaling [2]. A recent study found that CD4+ T cells from SLE patients fail to upregulate BTLA upon activation [3], however, data on BTLA expression and function for B cells in autoimmunity is missing.ObjectivesTo assess BTLA expression on conventional naïve (CD20+CD27-), conventional memory (CD20+CD27+) B cells and on CD27++CD38++ expressing plasma cells (PC) in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) and healthy donors (HD).MethodsPBMCs were isolated from EDTA blood taken from 7 female SLE patients (age 38, mean disease activity 5 (SLEDAI)) and 6 female HD (mean age 28) by Ficoll density gradient centrifugation according to the manufacturer’s protocol. Cells have been stained and expression of BTLA was assessed by flow cytometry.ResultsAnalysis of BTLA surface expression on B cell subsets in SLE patients and HD revealed decreased expression of BTLA on naïve SLE B cells (*p=0.0173, Mann-Whitney U Test (MWU), BTLA median fluorescence intensity (MFI) 9006±1450) compared to naïve HD B cells (11957±941). A similar tendency was found for memory SLE B cells (p=0.0823 MWU) compared to HD memory but not SLE PC and HD PC. Remarkably, an inverse correlation was found for BTLA expression on naïve SLE B cells and SLE PC with Siglec-1 expression on monocytes (*p=0.0333 Spearman’s rank correlation (SRC) naïve B cells, *p=0.0167 PC), a marker for interferon signature, and the same trend was seen for SLE memory B cells (p=0.0583 SRC). Inverse correlation of BTLA expression was also found with disease activity (SLEDAI) with these B cell populations but did not reach significance (p=0.0583 naïve B cells, p=0.1361 memory B cells, p=0.0833 PC).ConclusionHerein, we document that B cell subsets of SLE patients express lower levels of the negative regulator BTLA than HD. Additionally, an inverse correlation between BTLA expression on B cell subsets and Siglec-1 on monocytes were found suggesting its involvement in disease and consideration BTLA as therapeutic target in SLE. We hypothesize that reduced BTLA expression is a feature of post-activated B cells. Further studies need to delineate functional properties of BTLA expression and activation in autoimmune B cells.References[1] Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, Hurchla MA, Zimmerman N, Sim J, Zang X, et al: BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol 2003, 4(7):670-679.[2] Vendel AC, Calemine-Fenaux J, Izrael-Tomasevic A, Chauhan V, Arnott D, Eaton DL: B and T lymphocyte attenuator regulates B cell receptor signaling by targeting Syk and BLNK. J Immunol2009, 182(3):1509-1517.[3] Sawaf M, Fauny JD, Felten R, Sagez F, Gottenberg JE, Dumortier H, Monneaux F: Defective BTLA...

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The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy

Abstract: Our results suggest that Th17/Treg imbalance is characteristic of childhood IE, and may contribute to IE pathogenesis. KD treatment is able to correct this imbalance, probably via inhabiting the mTOR/HIF-1α signaling pathway.

Cited by 43 publications

References 25 publications

Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy

Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy

Ketogenic diets attenuate cyclooxygenase and lipoxygenase gene expression in multiple sclerosis

Ab0194 btla Expression Is Reduced on Sle B Cell Subsets

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