ニシオ　ジュンコ   Nishio Junko   西尾　純子    所属   東邦大学  医学部 医学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	HMGB1-mediated chromatin remodeling attenuates Il24 gene expression for the protection from allergic contact dermatitis.
掲載誌名	正式名：Proceedings of the National Academy of Sciences of the United States of America
掲載区分	国外
巻・号・頁	118(1)
著者・共著者	Naoyuki Senda,Hideyuki Yanai,Sana Hibino,Lei Li,Yu Mizushima,Tomomitsu Miyagaki,Mai Saeki,Yusuke Kishi,Sho Hangai,Junko Nishio,Makoto Sugaya,Tadatsugu Taniguchi,Shinichi Sato
発行年月	2021/01/05
概要	Dysregulation of inflammatory cytokines in keratinocytes promote the pathogenesis of the skin inflammation, such as allergic contact dermatitis (ACD). High-mobility group box 1 protein (HMGB1) has been implicated in the promotion of skin inflammation upon its extracellular release as a damage-associated molecular pattern molecule. However, whether and how HMGB1 in keratinocytes contributes to ACD and other skin disorders remain elusive. In this study, we generated conditional knockout mice in which the Hmgb1 gene is specifically deleted in keratinocytes, and examined its role in ACD models. Interestingly, the mutant mice showed exacerbated skin inflammation, accompanied by increased ear thickening in 2,4-dinitrofluorobenezene-induced ACDs. The mRNA expression of interleukin-24 (IL-24), a cytokine known to critically contribute to ACD pathogenesis, was elevated in skin lesions of the mutant mice. As with constitutively expressed, IL-4-induced Il24 mRNA, expression was also augmented in the Hmgb1-deficient keratinocytes, which would account for the exacerbation of ACD in the mutant mice. Mechanistically, we observed an increased binding of trimethyl histone H3 (lys4) (H3K4me3), a hallmark of transcriptionally active genes, to the promoter region of the Il24 gene in the hmgb1-deficient cells. Thus, the nuclear HMGB1 is a critical "gate keeper" in that the dermal homeostasis is contingent to its function in chromatin remodeling. Our study revealed a facet of nuclear HMGB1, namely its antiinflammatory function in keratinocytes for the skin homeostasis.
DOI	10.1073/pnas.2022343118
PMID	33443188