Recruitment of Regulatory Lymphocytes Attenuates Periodontal Disease Symptoms

Objective: Periodontal disease is characterized by destructive inflammation of the periodontium (gum tissue and supporting bone and ligament) and is considered the most pressing oral health concern today, affecting over 78 million Americans.  Several invasive bacteria species are thought to trigger an excessive inflammatory immune reaction responsible for the soft and hard tissue destruction.  Current periodontal disease therapies focus on elimination of the invasive bacteria through clinical procedures known as scaling and root planing and, in severe cases, the use of local antibiotics.  However, recent literature suggests that although the bacteria initiate periodontal disease, symptoms are perpetuated by an imbalanced immune response.  Indeed, recent data indicates that periodontal lesions can be characterized an absence of a subset of lymphocytes that mediates immunological tolerance and homeostasis.   We hypothesize that recruiting regulatory lymphocytes back into the periodontium may not only decrease the symptoms of periodontal disease, but also restore immunological homeostasis and possibly even promote tissue regeneration. 

Methods: Poly(lactic-co-glycolic) acid (PLGA) controlled release microparticles were fabricated using a double emulsion procedure to encapsulate and sustain a biological gradient of the regulatory lymphocyte recruiting chemokine, CCL-22.  Briefly, mice infected with Actinobacillus actinomycetemcomitans were treated with CCL22 microparticles or PLGA controls.  Alveolar bone loss and cytokine levels were quantified as primary outcomes for disease severity.

 Results:   We observed the recruitment of regulatory T cells to CCL22 microparticles (injected into the periodontium) in mice and the subsequent amelioration of disease symptoms. CCL22 treated animals had less alveolar bone resorption and lower expression of inflammatory mediators than controls.

Conclusions: These results support our hypothesis and suggest that treating the underlying immune dysfunction may lead to more efficacious and long lasting solutions for periodontal disease.