RvE1 Impacts the Gingival Inflammatory Infiltrate by Inhibiting the T Cell Response in Experimental Periodontitis

Abstract

Periodontitis is a chronic inflammatory disease associated with the formation of dysbiotic plaque biofilms and characterized by the progressive destruction of the alveolar bone. The transition from health to disease is characterized by a shift in periodontal immune cell composition, from mostly innate (neutrophils) to adaptive (T lymphocytes) immune responses. Resolvin E1 (RvE1) is a specialized pro-resolution mediator (SPMs), produced in response to inflammation, to enhance its resolution. Previous studies have indicated the therapeutic potential of RvE1 in periodontal disease; however, the impact of RvE1 in the microbial-elicited osteoclastogenic immune response remains uncharacterized in vivo. In the present study, we studied the impact of RvE1 on the gingival inflammatory infiltrate formation during periodontitis in a mouse model. First, we characterized the temporal-dependent changes of the main immune cells infiltrating the gingiva by flow cytometry. Then, we evaluated the impact of early or delayed RvE1 administration on the gingival immune infiltration and cervical lymph nodes composition. We observed a consistent inhibitory outcome on T cells -particularly effector T cells- and a protective effect on regulatory T cells (Tregs). Our data further demonstrated the wide range of actions of RvE1, its preventive role in the establishment of the adaptive immune response during inflammation, and bone protective capacity.

Resolvins as a Treatment Modality in Experimental Periodontitis: A Systematic Review of Preclinical Studies

“…The full-text screening of the remaining nine articles further eliminated five as they did not meet the eligibility criteria. Among the excluded studies, one study did not have a control group [38], one study evaluated Rv's effect in periapical periodontitis [27], and two were invitro studies [39,40]. Finally, five studies were included in this systematic review [28][29][30][31][32].…”

Humanized Mouse Models for the Study of Periodontitis: An Opportunity to Elucidate Unresolved Aspects of Its Immunopathogenesis and Analyze New Immunotherapeutic Strategies

“…The ligature-induced periodontitis model has been extensively reported in mice ( 20 , 23 , 29 , 32 – 35 , 53 , 54 , 60 ); however, the extremely small mice oral cavity and the minuscule interproximal space between the maxillary or mandibular molars represent a not minor technical difficulty in placing the ligatures ( 73 ). Moreover, this placement can get even harder when dealing with immunodeficient mice when working in sterile conditions; thus, reinforcing the idea that experienced and highly skilled operators are needed.…”

Quercetin Preserves Oral Cavity Health by Mitigating Inflammation and Microbial Dysbiosis

“…Oral swabs of teeth and gingival tissue were taken before the induction of periodontitis on day 1 and day 6 and final swabs were taken at the completion of the study on day 13. The gingival tissues around all maxillary molars, without including palatal or buccal mucosa, were carefully excised using a new sterile #15 scalpel blade under 3.5x magnification by a trained periodontist using Dental Loupes (38)(39)(40)(41). The mice were excluded from the study if the underlying bone was damaged during excision of the gingival tissues or the ligatures were lost.…”

“…Gingival tissues from Quercetin-treated and vehicle-treated control mice were removed using previously established protocols with slight modifications (44,55). Using a #15 scalpel blade and 3.5x magnification Dental Loupes, a trained periodontitis excised the gingival tissues surrounding the three maxillary molars on the ligated or control side of the maxilla without including buccal and palatal tissues and damaging underlying tissues or bone (38)(39)(40)(41). Tissues were fixed in 4% formaldehyde and sent to the Virginia Commonwealth University Cancer Mouse Models Core Laboratory where they were processed to paraffin.…”