Research report: Integrative transcriptomic and single-cell analyses link ENO1 to CD4+ T cell function and glycolysis-associated metabolism in systemic lupus erythematosus

Researchers have identified the glycolytic enzyme ENO1 as a leading candidate link between altered cellular metabolism and aberrant CD4+ T cell behaviour in systemic lupus erythematosus (SLE), a chronic autoimmune disease marked by immune dysregulation and enhanced glycolytic activity in CD4+ T cells. The study, published in Biology Direct, integrated bulk RNA sequencing data from peripheral blood mononuclear cells of SLE patients with a curated set of glycolysis- and lactate metabolism-related genes to prioritise candidate metabolic regulators.

The team first screened candidate genes against independent bulk RNA-seq datasets, then evaluated them in single-cell RNA sequencing data and in datasets from purified CD4+ T cells. ENO1 emerged as the top hit, reproducibly upregulated across multiple independent cohorts.

Single-cell analysis added a cellular dimension to the finding. CD4+ T cells from SLE patients showed elevated scores for the glycolysis- and lactate metabolism-related gene set, placing the metabolic shift specifically within the T cell compartment rather than reflecting bulk changes in blood composition. The authors note, however, that the molecular regulators connecting metabolic alterations to aberrant CD4+ T cell responses remain incompletely understood, and their work is framed as a resource for further mechanistic investigation.

To probe what ENO1 might be doing functionally, the researchers performed in silico perturbation analysis, which linked ENO1 to T-cell activation programs. They then tested these predictions experimentally: knocking down ENO1 altered the expression of activation-related genes including CCR7, IL7R, JUNB and AIF1. The perturbation results are computational predictions, but the downstream gene-expression changes were validated in laboratory experiments using human and murine CD4+ T cells.

Protein-level measurements supported the transcriptomic picture. ENO1 was elevated in PBMCs and in CD4+ T cells from SLE patients, and ENO1 expression in CD4+ T cells correlated positively with SLE Disease Activity Index (SLEDAI) scores, a clinical measure of disease activity. The correlation is an association observed in the studied samples and does not by itself establish that ENO1 drives disease severity.

Functional experiments pointed toward a role in T cell proliferation and metabolism. Inhibiting ENO1 suppressed the proliferation of both human and murine CD4+ T cells. In activated murine CD4+ T cells, ENO1 knockdown reduced glucose uptake and lowered intracellular lactate levels, consistent with ENO1’s established position in the glycolytic pathway. These are in vitro findings in isolated cells, not demonstrations of therapeutic effect in patients.

Because ENO1 sits at the intersection of immune activation and glucose metabolism, the authors also searched computationally for compounds that could interact with it. Molecular docking identified Barasertib and CC_401 as candidate ENO1-interacting compounds. The authors are explicit that this docking result provides only a computational basis for future validation; no compound activity against ENO1 in cells or in vivo has been demonstrated in this study.

By combining these layers, the authors positioned ENO1 not merely as a biomarker of SLE but as a candidate mechanistic node connecting glycolysis and lactate metabolism to CD4+ T cell activation programs.

Limitations remain. The clinical samples come from the patient cohorts analysed, the perturbation predictions are in silico, and the functional assays were conducted in isolated human and murine cells rather than in patients. The article itself is being shared early as a peer-reviewed, accepted version of record that is citable and carries a permanent DOI, subject to further editorial edits. The authors present the work as identifying ENO1 as a glycolysis- and lactate metabolism-associated factor associated with CD4+ T cell function in SLE, and as a resource for further mechanistic investigation of these metabolic pathways in the disease.

Subject of Research: The role of the glycolysis-related gene ENO1 in CD4+ T cell function in systemic lupus erythematosus

Article Title: Integrative transcriptomic and single-cell analyses link ENO1 to CD4+ T cell function and glycolysis-associated metabolism in systemic lupus erythematosus

Article References: Dong, W., Ma, Z., Jia, Y., Ji, D., Zeng, L., & Yi, H. (2026). Integrative transcriptomic and single-cell analyses link ENO1 to CD4+ T cell function and glycolysis-associated metabolism in systemic lupus erythematosus. Biology Direct. https://doi.org/10.1186/s13062-026-01036-3

Image Credits: AI Generated

DOI: 10.1186/s13062-026-01036-3

Keywords: systemic lupus erythematosus, ENO1, CD4+ T cells, glycolysis, lactate metabolism, single-cell RNA sequencing, transcriptomics, SLEDAI, molecular docking, autoimmunity, Integrative, transcriptomic