title: Vitamin C enhances the expression of IL17 in a Jmjd2-dependent manner.
abstract: Previously, we reported that vitamin C facilitates the CpG demethylation of Foxp3 enhancer in CD4＋Foxp3＋ regulatory T cells (Tregs) by enhancing the activity of a DNA demethylase ten-eleven-translocation (Tet). However, it is not clear whether vitamin C affects other helper T cell lineages like T helper type 17 (Th17) cells which are related with Tregs. Here, we show that the expression of interleukin-17A (IL17) increases with the treatment of vitamin C but not with other antioxidants. Interestingly, the upregulation of IL17 was not accompanied by DNA demethylation in Il17 promoter and was independent of Tet enzymes. Rather, vitamin C reduced the trimethylation of histone H3 lysine 9 (H3K9me3) in the regulatory elements of the Il17 locus, and the effects of vitamin C were abrogated by knockdown of jumonji-C domain-containing protein 2 (jmjd2). These results suggest that vitamin C can affect the expression of IL17 by modulating the histone demethylase activity. [BMB Reports 2017; 50(1): 49-54].
authors.affiliation: Department of Pathology, Hallym University College of Medicine, Chuncheon 24252, Korea.
authors.forename: Mi Hye
authors.initials: MH
authors.lastname: Song
authors.affiliation: Department of Pathology, Hallym University College of Medicine, Chuncheon 24252, Korea.
authors.forename: Varun Sasidharan
authors.initials: VS
authors.lastname: Nair
authors.affiliation: Department of Pathology, Hallym University College of Medicine, Chuncheon 24252, Korea.
authors.forename: Kwon Ik
authors.initials: KI
authors.lastname: Oh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D006657:Histones; C098680:Il17a protein, mouse; D020381:Interleukin-17; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C551914:Tet2 protein, mouse; D056466:Histone Demethylases; C560307:JMJD2A protein, mouse; D001205:Ascorbic Acid