Cellular Metabolic Heterogeneity and Therapeutic Targeting in Rheumatoid Arthritis
- 1Department of Rehabilitation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 2Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
- 3Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China
Abstract
Metabolic abnormalities in rheumatoid arthritis (RA) differ across cell populations and anatomical compartments. Glycolytic synovial fibroblasts coexist with blood T-cell populations showing impaired glycolytic induction or mitochondrial function, while macrophage metabolism can sustain inflammation or tissue protection. These differences complicate systemic metabolic inhibition. This narrative review integrates human RA studies, experimental arthritis and mechanistic work in other systems to identify dependencies that support defined pathogenic functions. We examine metabolite transport, nutrient adaptation and nutrient and energy sensing, distinguishing causal perturbation from descriptive signatures and preclinical hypotheses from clinical efficacy signals. Systemic cardiometabolic disease and nutritional interventions provide a clinical context for interpreting local metabolic findings. Small trials of repurposed drugs suggest possible benefit during treatment, but do not establish durable metabolic correction. We propose that a claim of reprogramming requires persistent functional change after drug removal, exclusion of residual exposure and selective cell loss, and preservation of immune regulation and host defence. These criteria could guide more selective metabolic interventions and their evaluation in patient tissue.
Related
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BibTeX
@article{chen2026cellular,
title = {{Cellular Metabolic Heterogeneity and Therapeutic Targeting in Rheumatoid Arthritis}},
author = {Sheng Chen and Yufan Luo and Qiuzhi Zhou and Hong Chen},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211949},
url = {https://www.mdpi.com/2073-4409/15/21/1949},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Cellular Metabolic Heterogeneity and Therapeutic Targeting in Rheumatoid Arthritis
AU - Sheng Chen
AU - Yufan Luo
AU - Qiuzhi Zhou
AU - Hong Chen
PY - 2026
DA - 2026/10/26
JO - Cells
DO - 10.3390/cells15211949
UR - https://www.mdpi.com/2073-4409/15/21/1949
AB - Metabolic abnormalities in rheumatoid arthritis (RA) differ across cell populations and anatomical compartments. Glycolytic synovial fibroblasts coexist with blood T-cell populations showing impaired glycolytic induction or mitochondrial function, while macrophage metabolism can sustain inflammation or tissue protection. These differences complicate systemic metabolic inhibition. This narrative review integrates human RA studies, experimental arthritis and mechanistic work in other systems to identify dependencies that support defined pathogenic functions. We examine metabolite transport, nutrient adaptation and nutrient and energy sensing, distinguishing causal perturbation from descriptive signatures and preclinical hypotheses from clinical efficacy signals. Systemic cardiometabolic disease and nutritional interventions provide a clinical context for interpreting local metabolic findings. Small trials of repurposed drugs suggest possible benefit during treatment, but do not establish durable metabolic correction. We propose that a claim of reprogramming requires persistent functional change after drug removal, exclusion of residual exposure and selective cell loss, and preservation of immune regulation and host defence. These criteria could guide more selective metabolic interventions and their evaluation in patient tissue.
SN - 2073-4409
ER -