title: IFN-gamma-STAT1 signal regulates the differentiation of inducible Treg: potential role for ROS-mediated apoptosis.
abstract: Regulatory CD4(+) T cells are important for the homeostasis of immune cells, and their absence correlates with autoimmune disorders. However, how the immune system regulates Treg homeostasis remains unclear. We found that IFN-gamma-deficient-mice had more forkhead box P3 (FOXP3(+)) cells than WT mice in all secondary lymphoid organs except the thymus. However, T-bet- or IL-4Ralpha-deficient mice did not show a similar increase. In vitro differentiation studies showed that conversion of naïve T cells into FOXP3(+) cells (neo-generated inducible Treg (iTreg)) by TGF-beta was significantly inhibited by IFN-gamma in a STAT-1-dependent manner. Moreover, an in vivo adoptive transfer study showed that inhibition of FOXP3(+) iTreg generation by IFN-gamma was a T-cell autocrine effect. This inhibitory effect of IFN-gamma on iTreg generation was significantly abrogated after N-acetyl-L-cysteine treatment both in vitro and in vivo, indicating that IFN-gamma regulation of iTreg generation is dependent on ROS-mediated apoptosis. Therefore, our results suggest that autocrine IFN-gamma can negatively regulate the neo-generation of FOXP3(+) iTreg through ROS-mediated apoptosis in the periphery.
authors.affiliation: Laboratory of Immunology, Department of Molecular Medicine and Biopharmaceutical Science, College of Pharmacy, Seoul National University, Gwanak-gu, Seoul, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Chang
authors.forename: Yeon-Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Han
authors.forename: Chang-Yuil
authors.initials: CY
authors.lastname: Kang