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Enhanced Fatty Acid Synthesis Leads to Subset Imbalance and IFN-γ Overproduction in T Helper 1 Cells.

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收录情况： ◇ SCIE

作者：
Iwata Shigeru[1] * ; Zhang Mingzeng[1,2] ; Hao He[1,3] ; Trimova Gulzhan[1,4] ; Hajime Maiko[1] ; Miyazaki Yusuke[1] ; Ohkubo Naoaki[1] ; Satoh Kanda Yurie[1] ; Todoroki Yasuyuki[1] ; Miyata Hiroko[1] ; Ueno Masanobu[1] ; Nagayasu Atsushi[1] ; Nakayamada Shingo[1] ; Sakata Kei[1,5] ; Tanaka Yoshiya[1] ;
机构： [1]The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan, [2]Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China, [3]Department of Immuno-oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China, [4]Department of Clinical Subjects, High School of Medicine, Faculty of Medicine and Health Care, Al-Farabi Kazakh National University, Almaty, Kazakhstan, [5]Research Unit/Immunology & Inflammation, Innovative Research Division, Mitsubishi Tanabe Pharma, Yokohama, Japan
出处：
DOI： 10.3389/fimmu.2020.593103
ISSN：

关键词： systemic lupus erythematosus T-bet IFN-g fatty acid synthesis immunometabolism

摘要：
Recent reports have shown the importance of IFN-γ and T-bet+ B cells in the pathology of SLE, suggesting the involvement of IFN-γ-producing T-bet+ CD4+ cells, i.e., Th1 cells. This study determined the changes in Th1 subsets with metabolic shift and their potential as therapeutic targets in SLE. Compared with healthy donors, patients with SLE had higher numbers of T-bethiCXCR3lo effector cells and T-bet+Foxp3lo non-suppressive cells, which excessively produce IFN-γ, and lower number of non-IFN-γ-producing T-bet+Foxp3hi activated-Treg cells. These changes were considered to be involved in treatment resistance. The differentiation mechanism of Th1 subsets was investigated in vitro using memory CD4+ cells obtained from healthy donors and patients with SLE. In memory CD4+ cells of healthy donors, both rapamycin and 2-deoxy-D-glucose (2DG) suppressed T-bet+Foxp3- cells, and induced T-bet+Foxp3+(lo/hi) cells. Rapamycin induced IFN-γ-producing T-bet+Foxp3lo cells accompanied with enhanced lipid metabolism, whereas 2DG induced IFN-γ-non-producing T-bet+Foxp3hi cells. In memory CD4+ cells of SLE patients, inhibition of fatty acid synthesis, but not β-oxidation, suppressed IFN-γ production, and up-regulated of Foxp3 expression in T-bet+Foxp3+ cells. Metabolic regulators such as fatty acid synthesis inhibitors may improve the pathological status by correcting Th1 subset imbalance and overproduction of IFN-γ in SLE. Copyright © 2020 Iwata, Zhang, Hao, Trimova, Hajime, Miyazaki, Ohkubo, Satoh Kanda, Todoroki, Miyata, Ueno, Nagayasu, Nakayamada, Sakata and Tanaka.

基金：
This work was supported in part by JSPS KAKENHI grant number #JP16K09928 and the University of Occupational and Environmental Health, Japan, through UOEH Grant for Advanced Research (#H29-903 and #H30-905).
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外文
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出版当年[2020]版：
大类 | 2 区 医学
小类 | 2 区 免疫学
最新[2025]版：
大类 | 2 区 医学
小类 | 2 区 免疫学
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出版当年[2020]版：
Q1 IMMUNOLOGY
最新[2024]版：
Q1 IMMUNOLOGY

影响因子： 最新[2024版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]The First Department of Internal Medicine, School of Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan,
通讯作者：
推荐引用方式(GB/T 7714)：
Iwata Shigeru,Zhang Mingzeng,Hao He,et al.Enhanced Fatty Acid Synthesis Leads to Subset Imbalance and IFN-γ Overproduction in T Helper 1 Cells.[J].FRONTIERS IN IMMUNOLOGY.2020,11:doi:10.3389/fimmu.2020.593103.
APA：
Iwata Shigeru,Zhang Mingzeng,Hao He,Trimova Gulzhan,Hajime Maiko...&Tanaka Yoshiya.(2020).Enhanced Fatty Acid Synthesis Leads to Subset Imbalance and IFN-γ Overproduction in T Helper 1 Cells..FRONTIERS IN IMMUNOLOGY,11,
MLA：
Iwata Shigeru,et al."Enhanced Fatty Acid Synthesis Leads to Subset Imbalance and IFN-γ Overproduction in T Helper 1 Cells.".FRONTIERS IN IMMUNOLOGY 11.(2020)

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