期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.593103
关键词
systemic lupus erythematosus; T-bet; IFN-γ fatty acid synthesis; immunometabolism
类别
资金
- JSPS KAKENHI [JP16K09928]
- University of Occupational and Environmental Health, Japan through UOEH Grant for Advanced Research [H29-903, H30-905]
Recent reports have shown the importance of IFN-gamma and T-bet(+) B cells in the pathology of SLE, suggesting the involvement of IFN-gamma-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-bet(hi)CXCR3(lo) effector cells and T-bet(+)Foxp3(lo) non-suppressive cells, which excessively produce IFN-gamma, and lower number of non-IFN-gamma-producing T-bet(+)Foxp3(hi) activated-T-reg 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-gamma-producing T-bet(+)Foxp3(lo) cells accompanied with enhanced lipid metabolism, whereas 2DG induced IFN-gamma-non-producing T-bet(+)Foxp3(hi) cells. In memory CD4(+) cells of SLE patients, inhibition of fatty acid synthesis, but not beta-oxidation, suppressed IFN-gamma 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-gamma in SLE.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据