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<p>Cell metabolism is an indispensable biochemical process that provides the basic energy and materials necessary for normal cell function. Accumulating evidence implicates abnormal metabolism of T cells as playing a critical role in the pathogenesis of rheumatoid arthritis (RA). The deacetylase SIRT3 has been shown to directly regulate energy metabolism in nonimmune cells. However, the role of SIRT3 in T cells and whether it participates in RA process remain unclear. In this study, we demonstrated that T-cell glycolysis was inhibited after SIRT3 deficiency. Compared to wild-type mice, SIRT3 knockout mice exhibited more severe arthritis, cartilage erosion, and inflammation after immunization with antigen-induced arthritis (AIA). It is interesting to note that SIRT3 deficiency reduced the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and rate-limiting enzyme in glycolysis. Overexpression of PFKFB3 was shown to restore the impaired ATP production caused by SIRT3 deficiency in T cells, and protects T cells from apoptosis. In summary, SIRT3 plays an important role in the regulation of T-cell metabolism in the pathogenesis of RA. SIRT3 deficiency decreases glycolysis, reduces ATP production, induces apoptosis in CD4<sup>+</sup> T cells, and further promotes AIA in mice.</p>

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SIRT3 deficiency reduces PFKFB3-driven T-cell glycolysis and promotes arthritic inflammation

  • 期刊论文

  • 发表日期：

    2025年2月27日

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  • Ting-Ting Wang,
  • Taotao Han,
  • Xinyue Xiao,
  • Dan Guo,
  • Xin Sun,
  • Yudong Liu,
  • Lidan Zhao,
  • Haojie Xu,
  • Rong Li,
  • Lingjuan Jiang,
  • Bo Zhang,
  • Beidi Chen,
  • Shengru Wang,
  • Han Wang,
  • Xiaoxi Wang,
  • Miao Zhang,
  • Sumei Zhang,
  • Jian Wang,
  • Jiahua Qu,
  • Hou-Zao Chen,
  • De-Pei Liu,
  • Xuan Zhang,
  • Min Wang

摘要

Cell metabolism is an indispensable biochemical process that provides the basic energy and materials necessary for normal cell function. Accumulating evidence implicates abnormal metabolism of T cells as playing a critical role in the pathogenesis of rheumatoid arthritis (RA). The deacetylase SIRT3 has been shown to directly regulate energy metabolism in nonimmune cells. However, the role of SIRT3 in T cells and whether it participates in RA process remain unclear. In this study, we demonstrated that T-cell glycolysis was inhibited after SIRT3 deficiency. Compared to wild-type mice, SIRT3 knockout mice exhibited more severe arthritis, cartilage erosion, and inflammation after immunization with antigen-induced arthritis (AIA). It is interesting to note that SIRT3 deficiency reduced the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and rate-limiting enzyme in glycolysis. Overexpression of PFKFB3 was shown to restore the impaired ATP production caused by SIRT3 deficiency in T cells, and protects T cells from apoptosis. In summary, SIRT3 plays an important role in the regulation of T-cell metabolism in the pathogenesis of RA. SIRT3 deficiency decreases glycolysis, reduces ATP production, induces apoptosis in CD4+ T cells, and further promotes AIA in mice.