Exploration of Immunology

Table 2. Distinct Treg subsets and their epigenetic-metabolic features in rheumatic disease.

Treg subset	Functional state	Dominant metabolic features	Key epigenetic features	Relevance in rheumatic disease
Resting/naïve-like Tregs	Baseline suppressive maintenance	OXPHOS, FAO, mitochondrial fitness	Stable FOXP3 demethylation; repressive inflammatory chromatin	Maintenance of systemic tolerance
Activated/effector Tregs	Tissue-adapted suppression, proliferation, migration	Mixed oxidative metabolism with controlled glycolytic support	Adaptive chromatin remodeling at trafficking and suppressive loci	Active suppression in inflamed tissues, such as the RA synovium
Unstable/ex-Tregs	Loss of suppressive identity; inflammatory conversion	Glycolytic bias, ROS accumulation, mitochondrial dysfunction	FOXP3 instability; permissive inflammatory chromatin	Treg dysfunction and pathogenic plasticity in chronic inflammation

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FAO: fatty-acid oxidation; FOXP3: forkhead box P3; OXPHOS: oxidative phosphorylation; RA: rheumatoid arthritis; ROS: reactive oxygen species; Tregs: regulatory T cells.

Declarations

Author contributions

OAA: Conceptualization, Investigation, Visualization, Writing—original draft. MMN: Conceptualization, Investigation, Methodology, Project administration, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. Both authors read and approved the submitted version.

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The authors declare no conflict of interest.

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