title: The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy.
abstract: OBJECTIVE
  The ketogenic diet (KD) is an effective treatment for intractable epilepsy (IE), however the therapeutic mechanism is still unclear. This study was designed to investigate T helper type 17/regulatory T cell (Th17/Treg) levels in children with IE and age-matched healthy controls following KD.
  
  
  METHODS
  Circulating levels of Th17/Treg cells were analyzed by flow cytometry. Plasma concentration of interleukin (IL)-17 was measured by cytometric bead array assay. Real-time PCR was performed to measure mRNA levels of mTOR, HIF1α and Th17/Treg associated factors in purified CD4(+)CD25(+) T and CD4(+)CD25(-) T cells.
  
  
  RESULTS
  By one-way ANOVA, the proportion of circulating Th17 cells and expression of IL-17A and RORγt were significantly higher (P<.05), while the proportion of circulating Tregs and expression of Foxp3, GITR, CTLA-4 were significantly lower (P<.05) in IE patients than healthy subjects. However, these alternations were reversed following KD (P<.05). In CD4(+)CD25(+) T and CD4(+)CD25(-) T cells mTOR and HIF1α expression were significantly higher in IE patients (P<.05), however KD reduced mTOR and HIF1α expression (P<.05). The plasma IL-17A concentrations were higher in IE patients than controls (P<.05). KD partially reduced IL-17A levels (P<.05).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Ni
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China. Electronic address: shenzhen81111@163.com.
authors.forename: Cheng-Rong
authors.initials: CR
authors.lastname: Li
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Jian-Xiang
authors.initials: JX
authors.lastname: Liao
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Guo-Bing
authors.initials: GB
authors.lastname: Wang
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Lin
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Institute of Pediatrics, Shenzhen Children's Hospital, Shenzhen 518026, China.
authors.forename: Jia-Lun
authors.initials: JL
authors.lastname: Wen
mesh_terms: D002648:Child; D002675:Child, Preschool; D055423:Diet, Ketogenic / Q000379:methods*; D000069279:Drug Resistant Epilepsy / Q000097:blood* / Q000178:diet therapy*; D005260:Female; D006801:Humans; D007223:Infant; D020381:Interleukin-17 / Q000097:blood*; D008297:Male; D050378:T-Lymphocytes, Regulatory; D058504:Th17 Cells; D016896:Treatment Outcome
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17
keywords: Intractable epilepsy; Ketogenic diet; Th17 cells; Treg cells