オダ ヒデアキ   ODA Hideaki
  小田 秀明
   所属   医学部 医学科
   職種   教授・講座主任
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Acquired deficiency of A20 results in rapid apoptosis, systemic inflammation, and abnormal hematopoietic stem cell function.
掲載誌名 正式名:PloS one
略  称:PLoS One
ISSNコード:(1932-6203)1932-6203(Linking)
掲載区分国外
巻・号・頁 9(1),e87425頁
著者・共著者 Nagamachi Akiko, Nakata Yuichiro, Ueda Takeshi, Yamasaki Norimasa, Ebihara Yasuhiro, Tsuji Kohichiro, Honda Zen-ichiro, Takubo Keiyo, Suda Toshio, Oda Hideaki, Inaba Toshiya, Honda Hiroaki
発行年月 2014
概要 A20 is a negative regulator of NF-κB, and mutational loss of A20 expression is involved in the pathogenesis of autoimmune diseases and B-cell lymphomas. To clarify the role of A20 in adult hematopoiesis, we generated conditional A20 knockout mice (A20(flox/flox) ) and crossed them with Mx-1Cre (MxCre (+)) and ERT2Cre (ERT2Cre (+)) transgenic mice in which Cre is inducibly activated by endogenous interferon and exogenous tamoxifen, respectively. A20(flox/flox) MxCre (+) (A20Mx) mice spontaneously exhibited myeloid proliferation, B cell apoptosis, and anemia with overproduction of pro-inflammatory cytokines. Bone marrow transplantation demonstrated that these changes were caused by hematopoietic cells. NF-κB was constitutively activated in A20Mx hematopoietic stem cells (HSCs), which caused enhanced cell cycle entry and impaired repopulating ability. Tamoxifen stimulation of A20(flox/flox) ERT2Cre (+) (A20ERT2) mice induced fulminant apoptosis and subsequent myeloproliferation, lymphocytopenia, and progressive anemia with excessive production of pro-inflammatory cytokines, as observed in A20Mx mice. These results demonstrate that A20 plays essential roles in the homeostasis of adult hematopoiesis by preventing apoptosis and inflammation. Our findings provide insights into the mechanism underlying A20 dysfunction and human diseases in which A20 expression is impaired.
DOI 10.1371/journal.pone.0087425
PMID 24498102