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オカモト ユウコ
OKAMOTO Yuuko
岡本 祐子 所属 医学部 医学科（東京女子医科大学病院） 職種 講師 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | A molecular signature of preclinical rheumatoid arthritis triggered by dysregulated PTPN22. |
| 掲載誌名 | 正式名：JCI insight 略 称：JCI Insight ISSNコード：23793708/23793708 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 1(17),pp.e90045 |
| 著者・共著者 | Chang Hui-Hsin, Liu Guang-Yaw, Dwivedi Nishant, Sun Bo, Okamoto Yuko, Kinslow Jennifer D, Deane Kevin D, Demoruelle M Kristen, Norris Jill M, Thompson Paul R, Sparks Jeffrey A, Rao Deepak A, Karlson Elizabeth W, Hung Hui-Chih, Holers V Michael, Ho I-Cheng |
| 発行年月 | 2016/10 |
| 概要 | A unique feature of rheumatoid arthritis (RA) is the presence of anti-citrullinated protein antibodies (ACPA). Several risk factors for RA are known to increase the expression or activity of peptidyl arginine deiminases (PADs), which catalyze citrullination and, when dysregulated, can result in hypercitrullination. However, the consequence of hypercitrullination is unknown and the function of each PAD has yet to be defined. Th cells of RA patients are hypoglycolytic and hyperproliferative due to impaired expression of PFKFB3 and ATM, respectively. Here, we report that these features are also observed in peripheral blood mononuclear cells (PBMCs) from healthy at-risk individuals (ARIs). PBMCs of ARIs are also hypercitrullinated and produce more IL-2 and Th17 cytokines but fewer Th2 cytokines. These abnormal features are due to impaired induction of PTPN22, a phosphatase that also suppresses citrullination independently of its phosphatase activity. Attenuated phosphatase activity of PTPN22 results in aberrant expression of IL-2, ATM, and PFKFB3, whereas diminished nonphosphatase activity of PTPN22 leads to hypercitrullination mediated by PADs. PAD2- or PAD4-mediated hypercitrullination reduces the expression of Th2 cytokines. By contrast, only PAD2-mediated hypercitrullination can increase the expression of Th17 cytokines. Taken together, our data depict a molecular signature of preclinical RA that is triggered by impaired induction of PTPN22. |
| DOI | 10.1172/jci.insight.90045 |
| PMID | 27777982 |