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. 2021 Feb 25;12:635021. doi: 10.3389/fimmu.2021.635021

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Copyright © 2021 Lin, Shen, Song, Huang and Tu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Different redox state between naïve CD4⁺ T cell and synovium in rheumatoid arthritis. In naïve CD4⁺ T cell of rheumatoid arthritis patients, glucose shunting into pentose phosphate pathway due to the change of metabolic key enzymes (PFKFB3 and G6PD) activity leads to a special microenvironment characterized by low ATP, high reducing equivalences (GSH and NADPH) and exhausted ROS. Whether glutaminolysis is associated with this remains to unclear. In contrast, synovium of patients experienced oxidative stress and abnormal aerobic glycolysis that result from hypoxia in the joint. These two split situation destruct joints together by the integration of up-regulated TKS5 in naïve CD4⁺ T cell and high lactates in synovium.