5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation
Year: 2020
Type: article
Abstract: While it is well established that treatment of cancer patients with 5-Fluorouracil (5-FU) can result in immune suppression, the exact function of 5-FU in the modulation of immune cells has not been fully established. We found that low dose 5-FU selectively suppresses TH17 and TH1 cell differentiation without apparent effect on Treg, TH2, and significantly suppresses thymidylate synthase (TS) expression in TH17 and TH1 cells but has a lesser effect in tumor cells and macrophages. Interestingly, the basal expression of TS varies significantly between T helper phenotypes and knockdown of TS significantly impairs TH17 and TH1 cell differentiation without affecting the differentiation of either Treg or TH2 cells. Finally, low dose 5-FU is effective in ameliorating colitis development by suppressing TH17 and TH1 cell development in a T cell transfer colitis model. Taken together, the results highlight the importance of the anti-inflammatory functions of low dose 5-FU by selectively suppressing TH17 and TH1 immune responses.
DOI: 10.17615/m5rw-zf75
Authors: Chen, Shu-Hsia, Xiong, Huabao, Yang, Jianjun, Cui, Miao, Xu, Feihong, Li, Liwu, Jiang, Bo, Sikora, Andrew G., Zheng, Zihan, Hu, Yuan, Lu, Geming, Cheung, Ka Lung, Chen, Chun, Zhang, Ruihua, Zhou, Ming-Ming, Bian, Guanglin, Zhu, Hongfa, Peng, Liang, Liu, Kebin, Chiang, David, Chen, Ye, Wang, Juan, Zhang, Hui, Yang, Jianfei
Institution: University of North Carolina at Chapel Hill
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W4298369197