Cell Metabolism: Significant progress! Chi Hongbo's team revealed metabolic mechanisms that regulate Treg cells or provide new targets for autoimmune disease therapy

Effect-regulated T (eTreg) cells are critical to immune tolerance, and understanding the regulatory mechanisms for eTreg cell differentiation and maintenance is important for autoimmune diseases, cancers, and infectious diseases.
, however, it is not clear how metabolic pathways regulate eTreg cell differentiation and maintenance.
Professor Chi Hongbo of St. Jude Children's Research Hospital in the United States published the results of the study online on Cell Metabolism, entitled Protein Prenylation Drives Discrete Signaling Programs for The Sourceion Maintenance of Effector Treg Cells.
the study sheds light on the crucial role of isoprene modification after translation of metabolic dependence in immunosuppression mediated by eTreg cells.
study of content-regulated T (Treg) cells is critical to building autoimmune tolerance, which depends on the transformation of Treg (cTreg) cells in the central Treg (eTreg) cells during steady-state and inflammatory processes.
eTreg cells showed excellent inhibitory activity and increased tolerance to non-lymphatic tissue compared to cTreg cells.
the function of Treg cells, but the specific metabolic procedures that support eTreg cells are unclear.
authors found that the expression of multiple genes involved in the mediated cholesterol biosynthetic and isoprene-like dependence translation of lipid modification increased in the active Treg cells compared to resting Treg cells.
TCR activation induced changes in gene expression in the pathways of methyluxylurene and isoprene-like dependence protein isoprene.
photo source: Cell Metabolism, due to isoprene-like mediated protein isoprene, the authors then tested whether isoprene-like isoprene has established Treg cell function through translational lipid modification.
After the conditional knockout of the Fntb or Pggt1b gene in the Treg cells of mice, the mice showed signs of short stature, systemic inflammation and rapid death, indicating that Fntb and Pggt1b in Treg cells had a role in controlling immune stability.
image source: Cell Metabolism further studies have found that Fntb and Pggt1b are critical to the accumulation of eTreg cells, but these two genes regulate different aspects of eTreg cell stabilization.
Fntb is essential for cTreg cell activation and differentiation into eTreg cells, but may contribute to the maintenance of eTreg cells, while Pggt1b promotes eTreg cell differentiation during cTreg cell activation.
to explore the mechanism of eTreg cell maintenance on which Fntb depends, the authors found a significant decrease in mTORC1 activation after Fntb was inhibited, using GSEA analysis.
further experiments confirm that Fntb, rather than Pggt1b, is critical for the activation of mTORC1 in TCR-stimulated cTreg cells.
photo source: Cell MetabolismGGTI (Inhibit Pggt1b) Handles the upward adjustment of CD5 and Nur77-GFP after TCR activation that inhibits cTreg cells, indicating that Pggt1b tunes the TCR signal.
addition, in order to receive TCR signals, Treg cells interact with antigen-presented degeneral cells (DCs) in the T cell region.
Pggt1b defective Treg cells are less adhesive to dc, and more obvious defects have been observed in eTreg cells, indicating that Pggt1b is essential to promote the adhesion of Treg cells to DC.
photo source: Cell Metabolism In order to identify possible molecular targets for Pggt1b, the authors used an original approach to analysis that predicted several classical pathways in Pggt1b defective Treg cells, including Rac signal conduction.
further experiments have shown that Rac signals contribute to TCR dependency activation and eTreg cell differentiation downstream of Pggt1b.
Photo Source: Cell Metabolism Study Summary Image Source: Cell Metabolism In this study, the authors found a two-way metabolic signaling mechanism between immune subjects and metabolic dependence modification during eTreg cell differentiation and maintenance.
Specifically, the inhibitory activity of isoprene-like establishment activated Treg derived from the metabolic pathways of methyluxyrene, as well as isoprene-dependent proteins, isfanikirification and balsamic leafylation, which are required for immune tolerance, and these processes are mediated by Fntb and Pggt1b, respectively.
addition, the authors identified specific catalytic effects of Fntb on mTORC1 activity and ICOS expression to maintain eTreg cells, while Pggt1b mediates TCR activation and Rac signal conduction eTreg cell differentiation.
study identified a key link between cell metabolism and lipid modification after protein translation necessary for eTreg cell differentiation and maintenance.
findings that Fntb and Pggt1b regulate different signaling path paths and cellular function may provide potential targets for selectively regulating Treg cell activity in autoimmune diseases, cancers, and infectious diseases.
"We can study how metabolic regulation controls the differentiation and maintenance of eTreg cells," says Wei Su, author of the article, "This two-way interaction between in-cell signaling and metabolism enables eTreg cells to maintain self-tolerance in our bodies."
"These pathways, as a way to suppress inflammatory responses and outside the immune system, have been the focus of attention, and our study provides new insights into the molecular interactions between signals and metabolism, helping to make the metabolic function of the lower and middle levels of Treg cells more effective and targeted.
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