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<p>Regulatory T (T<sub>reg</sub>) cells are considered as key regulators of adipose homeostasis and metabolic health. However, the underlying regulatory mechanisms remain unclear. Here we show that expression of G-protein-signaling modulator 1 (GPSM1) in CD4<sup>+</sup> T cells in peripheral blood and visceral fat is significantly upregulated in humans upon obesity and glucose dysregulation. Genomic deletion of GPSM1 in CD4<sup>+</sup> T cells or T<sub>reg</sub> cells in mice results in increased numbers of T<sub>reg</sub> cells in adipose tissues, restrained inflammation and improved insulin and glucose tolerance upon feeding with high fat diet. These metabolic changes are mediated by the maintenance of a specific CD73<sup>+</sup>CD103<sup>+</sup> T<sub>reg</sub> cell subpopulation. By contrast, mice with CD4<sup>+</sup> T-cell-specific overexpression of GPSM1 are characterized by decreased numbers of T<sub>reg</sub> cells and are more prone to adipose tissue dysfunction and metabolic deterioration. Mechanistically, a RHOA-cell stiffness-TAZ axis mediates the effects of GPSM1 on the abundance of T<sub>reg</sub> cells. Furthermore, adoptive transfer of GPSM1-deficent T<sub>reg</sub> cells promotes energy expenditure and improve glucose and lipid metabolism in <i>Rag1</i> <sup>−/−</sup> mice. In summary, GSPM1 expression in T<sub>reg</sub> cells and especially in a subset specialized for metabolic regulation is an important regulator of the overall energy homeostasis.</p>

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GPSM1 restricts CD73+CD103+ Treg cells in adipose tissue, critical for promoting obesity-related metabolic deterioration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月25日

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  • Xiao-Rui Lyu,
  • Rui-Bing Qi,
  • Yan-Li Hua,
  • Wei Chen,
  • Yi-Xuan Li,
  • Dai-Xi Wang,
  • Li-Jun Yao,
  • Hong-Li Chen,
  • Jiang-Fei Zheng,
  • Bao-Cheng Wan,
  • Yang Hua,
  • Feng Jiang,
  • Fan Yang,
  • Jia-Yu Ma,
  • Xiang-Hui Chen,
  • Rong Zhang,
  • Jing Yan,
  • Wei-Ping Jia,
  • Cheng Hu

摘要

Regulatory T (Treg) cells are considered as key regulators of adipose homeostasis and metabolic health. However, the underlying regulatory mechanisms remain unclear. Here we show that expression of G-protein-signaling modulator 1 (GPSM1) in CD4+ T cells in peripheral blood and visceral fat is significantly upregulated in humans upon obesity and glucose dysregulation. Genomic deletion of GPSM1 in CD4+ T cells or Treg cells in mice results in increased numbers of Treg cells in adipose tissues, restrained inflammation and improved insulin and glucose tolerance upon feeding with high fat diet. These metabolic changes are mediated by the maintenance of a specific CD73+CD103+ Treg cell subpopulation. By contrast, mice with CD4+ T-cell-specific overexpression of GPSM1 are characterized by decreased numbers of Treg cells and are more prone to adipose tissue dysfunction and metabolic deterioration. Mechanistically, a RHOA-cell stiffness-TAZ axis mediates the effects of GPSM1 on the abundance of Treg cells. Furthermore, adoptive transfer of GPSM1-deficent Treg cells promotes energy expenditure and improve glucose and lipid metabolism in Rag1 −/− mice. In summary, GSPM1 expression in Treg cells and especially in a subset specialized for metabolic regulation is an important regulator of the overall energy homeostasis.