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KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver.

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收录情况： ◇ SCIE

作者：
Wara Akm Khyrul[1] * ; Wang Shijia[1,2] * ; Wu Chun[1,2] ; Fang Fang[1,3] ; Haemmig Stefan[1] ; Weber Brittany N[1] ; Aydogan Ceren O[1,4] ; Tesmenitsky Yevgenia[1] ; Aliakbarian Hassan[5] ; Hawse John R[6] ; Subramaniam Malayannan[6] ; Zhao Lei[7] ; Sage Peter T[8] ; Tavakkoli Ali[4] ; Garza Amanda[9] ; Lynch Lydia[9] ; Banks Alexander S[10] ; Feinberg Mark W[1] ;
机构： [1]Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [2]Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China [3]Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, China [4]Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Cerrahpasa District, Kocamustafapasa Street, Number 34/E, Fatih, Istanbul, Turkey [5]Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [6]Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA [7]Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [8]Transplantation Research Center, Renal Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA [9]Department of Medicine, Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Boston, MA 02115, USA [10]Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
出处：
DOI： 10.1016/j.celrep.2020.108550
ISSN：

摘要：
CD4+ T cells regulate inflammation and metabolism in obesity. An imbalance of CD4+ T regulatory cells (Tregs) is critical in the development of insulin resistance and diabetes. Although cytokine control of this process is well understood, transcriptional regulation is not. KLF10, a member of the Kruppel-like transcription factor family, is an emerging regulator of immune cell function. We generated CD4+-T-cell-specific KLF10 knockout (TKO) mice and identified a predisposition to obesity, insulin resistance, and fatty liver due to defects of CD4+ Treg mobilization to liver and adipose tissue depots and decreased transforming growth factor β3 (TGF-β3) release in vitro and in vivo. Adoptive transfer of wild-type CD4+ Tregs fully rescued obesity, insulin resistance, and fatty liver. Mechanistically, TKO Tregs exhibit reduced mitochondrial respiration and glycolysis, phosphatidylinositol 3-kinase (PI3K)-Akt-mTOR signaling, and consequently impaired chemotactic properties. Collectively, our study identifies CD4+ T cell KLF10 as an essential regulator of obesity and insulin resistance by altering Treg metabolism and mobilization. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
NIH grants (HL115141, HL134849, HL148207, HL148355, and HL153356 to M.W.F.
语种：
外文
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中科院(CAS)分区：
出版当年[2019]版：
大类 | 1 区 生物
小类 | 2 区 细胞生物学
最新[2023]版：
大类 | 1 区 生物学
小类 | 2 区 细胞生物学
JCR分区：
出版当年[2018]版：
Q1 CELL BIOLOGY
最新[2023]版：
Q1 CELL BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

第一作者：
第一作者机构： [1]Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Wara Akm Khyrul,Wang Shijia,Wu Chun,et al.KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver.[J].CELL REPORTS.2020,33(13):doi:10.1016/j.celrep.2020.108550.
APA：
Wara Akm Khyrul,Wang Shijia,Wu Chun,Fang Fang,Haemmig Stefan...&Feinberg Mark W.(2020).KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver..CELL REPORTS,33,(13)
MLA：
Wara Akm Khyrul,et al."KLF10 Deficiency in CD4+ T Cells Triggers Obesity, Insulin Resistance, and Fatty Liver.".CELL REPORTS 33..13(2020)

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