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The Role of Regulatory T Cells in Periodontitis With or Without Systemic Diseases: A Systematic Review

In brief

Review of 20 studies finds altered regulatory T-cell balance in periodontitis

Across 20 studies, periodontitis was associated with changes in regulatory T cells, pro-inflammatory T-helper 17 cells and related cytokines, including in people with systemic diseases. Some immune markers changed after periodontal treatment, but the evidence does not show that these shifts cause disease or support therapies targeting regulatory T cells; stronger prospective studies are needed.

Journal
International journal of molecular sciences (Q1)
Published
21 September 2026
Study design
Systematic review / meta-analysis of RCTs
Evidence level
Level 1, High (CEBM 1a)
Authors
Angelo Michele Inchingolo, Maria Celeste Fatone, Grazia Marinelli, Laura Ferrante, Francesca Calò, Andrea Palermo, et al.
PMID
42794842
DOI
10.3390/ijms27188415

Why clinicians should know about it

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Abstract

Periodontitis is a chronic immune-mediated inflammatory disease of the oral cavity, frequently linked to systemic conditions through complex immunological pathways. Regulatory T lymphocytes (Tregs) are pivotal in maintaining immune homeostasis by producing anti-inflammatory mediators and enforcing self-tolerance. Recent research has highlighted their role in inflammatory, immune-mediated, and neoplastic diseases. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, exploring the role of Tregs in periodontitis, including patients with comorbidities such as type 2 diabetes mellitus, rheumatoid arthritis, atherosclerosis, and cancer, with a focus on cytokine profile alterations and therapeutic implications of Treg modulation. A systematic search of PubMed, Scopus, Web of Science, and Cochrane from January 2015 to August 2025 using "periodontitis" and "Tregs" or "regulatory T cells" yielded 20 studies. Available evidence suggests alterations in the balance between immunomodulatory Tregs and pro-inflammatory Th17 lymphocytes, together with changes in related cytokine profiles compared with healthy controls. Changes in Treg-related immune markers have also been reported following periodontal interventions; however, these findings do not establish a causal role for Treg modulation or support Treg-targeted therapies in current clinical practice. Well-designed prospective studies and, where appropriate, randomized controlled trials are required to strengthen causal and therapeutic inference.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.