The immune system is energetically demanding, and its activation, regulation, and dysfunction are intricately tied to metabolic reprogramming. In this issue of the Central European Journal of Immunology, Jin et al. present a significant contribution to our understanding of how altered glucose metabolism drives CD4+ T-cell dysfunction in systemic lupus erythematosus (SLE) [1].
Through comprehensive metabolic analyses, the authors demonstrate that CD4+ T cells from SLE patients exhibit a hypermetabolic state, marked by enhanced glycolysis and oxidative phosphorylation. These metabolic shifts are closely associated with disease flares and immune dysregulation. This study builds on a growing body of work within CEJI that emphasizes the immune-metabolic interface. For example, transcriptomic profiling by Wang et al. revealed that anaerobic glycolysis strongly influences Jurkat T-cell proliferation and gene expression signatures [2], offering foundational insight into T-cell bioenergetics under stress conditions. Moreover, recent work by Tao et al. highlighted how IL-17A, a cytokine implicated in autoimmunity, promotes glycolysis in hepatic stellate cells via the TRAF2/TRAF5/HuR/PFKFB3 axis, illustrating that immune-driven glycolysis is not restricted to lymphocytes, but extends to tissue remodeling and fibrosis [3].
Together, these findings suggest that dysregulated glucose metabolism is a common theme underlying both adaptive and tissue-resident immune cell dysfunction [4-6]. The work of Jin et al. distinguishes itself by directly linking these metabolic changes to clinical disease acti- vity in SLE, opening the door to novel metabolic interventions [1].
As immunometabolism continues to shape our understanding of autoimmunity and immune cell fate, this study stands out as a timely and mechanistically insightful contribution [7]. It reinforces the concept that targeted metabolic modulation, such as glycolysis inhibition, could complement immunosuppressive therapies in diseases like SLE.
