Periodontitis is an oral inflammatory disease in which the polymicrobial synergy and dysbiosis of the subgingival microbiota trigger a deregulated host immune response, that leads to the breakdown of tooth-supporting tissues and finally tooth loss. Periodontitis is characterized by the increased pathogenic activity of T helper type 17 (Th17) lymphocytes and defective immunoregulation mediated by phenotypically unstable T regulatory (Treg), lymphocytes, incapable of resolving the bone-resorbing inflammatory milieu. In this context, the complexity of the immune response orchestrated against the microbial challenge during periodontitis has made the study of its pathogenesis and therapy difficult and limited. Indeed, the ethical limitations that accompany human studies can lead to an insufficient etiopathogenic understanding of the disease and consequently, biased treatment decision-making. Alternatively, animal models allow us to manage these difficulties and give us the opportunity to partially emulate the etiopathogenesis of periodontitis by inoculating periodontopathogenic bacteria or by placing bacteria-accumulating ligatures around the teeth; however, these models still have limited translational application in humans. Accordingly, humanized animal models are able to emulate human-like complex networks of immune responses by engrafting human cells or tissues into specific strains of immunodeficient mice. Their characteristics enable a viable time window for the study of the establishment of a specific human immune response pattern in an in vivo setting and could be exploited for a wider study of the etiopathogenesis and/or treatment of periodontitis. For instance, the antigen-specific response of human dendritic cells against the periodontopathogen Porphyromonas gingivalis favoring the Th17/Treg response has already been tested in humanized mice models. Hypothetically, the proper emulation of periodontal dysbiosis in a humanized animal could give insights into the subtle molecular characteristics of a human-like local and systemic immune response during periodontitis and support the design of novel immunotherapeutic strategies. Therefore, the aims of this review are: To elucidate how the microbiota-elicited immunopathogenesis of periodontitis can be potentially emulated in humanized mouse models, to highlight their advantages and limitations in comparison with the already available experimental periodontitis non-humanized animal models, and to discuss the potential translational application of using these models for periodontitis immunotherapeutics.

This study aimed to analyze the root anatomy and root canal system morphology of mandibular first premolars in a Chilean population. 186 teeth were scanned using micro-computed tomography and reconstructed three-dimensionally. The root canal system morphology was classified using both Vertucci’s and Ahmed’s criteria. The radicular grooves were categorized using the ASUDAS system, and the presence of Tomes’ anomalous root was associated with Ahmed’s score. A single root canal was identified in 65.05% of teeth, being configuration type I according to Vertucci’s criteria and code 1MP1 according to Ahmed’s criteria. Radicular grooves were observed in 39.25% of teeth. The ASUDAS scores for radicular grooves were 60.75%, 13.98%, 12.36%, 10.22%, 2.15%, and 0.54%, from grade 0 to grade 5, respectively. The presence of Tomes’ anomalous root was identified only in teeth with multiple root canals, and it was more frequently associated with code 1MP1–2 of Ahmed’s criteria. The root canal system morphology of mandibular first premolars showed a wide range of anatomical variations in the Chilean population. Teeth with multiple root canals had a higher incidence of radicular grooves, which were closely related to more complex internal anatomy. Only teeth with multiple root canals presented Tomes’ anomalous root.

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Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4+ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28- Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4+CD28- T lymphocytes in periodontitis.