Full Papers
Obesity-exacerbated lupus via leptin-induced putrescine depletion and Tfh cell hyperactivation
M. Chen1, W. Chen2, Z. Zhao3, F. Jiao4, L. Song5, X. Zhao6, X. Chen7
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China.
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China.
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China.
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China.
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China.
- Department of Rheumatology and Immunology, Zhongnan Hospital of Wuhan University, Wuhan, China. chenxiaoqi@znhospital.cn
CER19722
Full Papers
PMID: 43001854 [PubMed]
Received: 23/01/2026
Accepted : 02/09/2026
In Press: 05/11/2026
Abstract
OBJECTIVES:
Obesity is a well-established risk factor exacerbating systemic lupus erythematosus (SLE). Although elevated leptin in obesity has been reported to regulate follicular helper T cells (Tfh) cell differentiation, relevant evidences remain inconsistent. The study explores whether obesity-induced hyperleptinaemia promotes SLE immunopathology via Tfh cell dysregulation and the underlying mechanism.
METHODS:
Serum leptin, cytokines, putrescine (PUT) and circulating Tfh (cTfh) cells were tested in healthy controls and SLE with active or remission state stratified by obesity. Leptin-treated Jurkat cells were analysed for programmed cell death protein 1 (PD-1) and metabolomics/transcriptomic profiling. The effects of ODC1 silencing and PUT treatment on Tfh-cell transcriptional regulators were evaluated in vitro.
RESULTS:
Leptin levels were significantly elevated in obese patients across all subgroups and correlated positively with autoantibodies. cTfh and activated cTfh frequencies were increased in remission patients compared to controls. Moreover, the frequencies were further elevated in obese patients and strongly correlated with leptin levels. Multiple cytokines were higher in SLE patients than healthy controls, furthermore, obesity could exacerbate the cytokine dysregulation. In vitro, leptin upregulated PD-1 expression in Jurkat cells and altered genes related to polyamine metabolism, particularly ornithine. Clinically, PUT levels were reduced in patients, especially with obesity. In vitro PUT deficiency increased Bcl-6 and decreased Blimp1, both reversible by PUT supplementation.
CONCLUSIONS:
Obesity-associated hyperleptinaemia could compound SLE via putrescine-implicated modulation of Tfh differentiation and concurrently contribute to a broad cytokine-driven inflammatory loop.
