5-Fluorouracil targets thymidylate synthase in the selective suppression of TH17 cell differentiation

Juan Wang1,2, Liang Peng2, Ruihua Zhang2

  • 1Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Oncotarget
|March 31, 2016
PubMed

Insights

Low dose 5-Fluorouracil (5-FU) selectively suppresses TH17 and TH1 immune responses by targeting thymidylate synthase (TS). This finding reveals 5-FU

Area of Science:

  • Immunology
  • Pharmacology
  • Cancer Biology

Background:

  • 5-Fluorouracil (5-FU) is a chemotherapy agent known to cause immune suppression in cancer patients.
  • The precise mechanisms by which 5-FU modulates immune cell function remain incompletely understood.

Purpose of the Study:

  • To elucidate the specific effects of low-dose 5-FU on immune cell differentiation and function.
  • To investigate the role of thymidylate synthase (TS) in 5-FU-mediated immune modulation.

Main Methods:

  • Treatment of immune cells with low-dose 5-FU.
  • Analysis of T helper cell differentiation (TH17, TH1, Treg, TH2).
  • Assessment of thymidylate synthase (TS) expression and function.
  • Utilizing a T cell transfer colitis model to evaluate in vivo efficacy.

Main Results:

  • Low-dose 5-FU selectively suppressed TH17 and TH1 cell differentiation, with minimal impact on Treg and TH2 cells.
  • 5-FU significantly reduced thymidylate synthase (TS) expression in TH17 and TH1 cells, more so than in tumor cells or macrophages.
  • TS knockdown impaired TH17 and TH1 differentiation, confirming its role in these T helper cell subsets.
  • Low-dose 5-FU ameliorated colitis in a mouse model by suppressing TH17 and TH1 cell development.

Conclusions:

  • Low-dose 5-FU exhibits significant anti-inflammatory properties by selectively targeting TH17 and TH1 immune responses.
  • The suppression of thymidylate synthase (TS) is a key mechanism underlying 5-FU's selective immunomodulatory effects.
  • These findings suggest potential therapeutic applications for low-dose 5-FU in inflammatory conditions.

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