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Updated: Nov 29, 2025

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector Treg Cells
Wei Su1, Nicole M Chapman2, Jun Wei2
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Science Program, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Abstract:
Effector regulatory T (eTreg) cells are essential for immune tolerance and depend upon T cell receptor (TCR) signals for generation. The immunometabolic signaling mechanisms that promote the differentiation and maintenance of eTreg cells remain unclear. Here, we show that isoprenoid-dependent posttranslational lipid modifications dictate eTreg cell accumulation and function by intersecting with TCR-induced intracellular signaling. We find that isoprenoids are essential for activated Treg cell suppressive activity, and Treg cell-specific deletion of the respective farnesylation- and geranylgeranylation-promoting enzymes Fntb or Pggt1b leads to the development of fatal autoimmunity, associated with reduced eTreg cell accumulation. Mechanistically, Fntb promotes eTreg cell maintenance by regulating mTORC1 activity and ICOS expression. In contrast, Pggt1b acts as a rheostat of TCR-dependent transcriptional programming and Rac-mediated signaling for establishment of eTreg cell differentiation and immune tolerance. Therefore, our results identify bidirectional metabolic signaling, specifically between immunoreceptor signaling and metabolism-mediated posttranslational lipid modifications, for the differentiation and maintenance of eTreg cells.
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