T-cell Responses Involved in the Predisposition to Periodontal Disease: Lessons from Immunogenetic Studies of Leprosy

Periodontitis, which involves loss of periodontal attachment and resorption of alveolar bone, is initially caused by infection with many kinds of anaerobic, gram-negative bacteria forming a subgingival biofilm. To prevent bacterial invasion, host defense mechanisms need to recruit many kinds of immunoregulatory cells, including helper T (Th) cells which play a central immune-regulatory role against periodontal infection. Similar to many infectious diseases, susceptibility to periodontal disease is partially determined by individual differences in Th cell responsiveness, especially cytokine production, against periodontopathic pathogens. Susceptibility to periodontitis has been associated with gene polymorphisms of several cytokines such as interleukin (IL)-2, IL-4, IL-6 and IL-10, but these correlations are predominantly weak due to their multifactorial nature. Distinct from these studies, we performed immunogenetic studies to investigate associations between periodontal disease susceptibility and hereditary cellmediated immune responses. In these studies, leprosy patients were used as a human model to understand the susceptibility to periodontitis, as leprosy is considered to be an infectious disease whose pathogenesis is regulated by diverse individually-inherited Th1/Th2 immune responses against the bacterial pathogen. In addition to the results of these studies, the discovery of a distinct Th17 lineage helps us to explain that disease susceptibility to periodontitis appears to be predominantly associated with the IL-23/IL-17 pathway. Therefore, individuals whose immunogenetic background is characterized as having low IL-12/interferon-γ activity may have a tendency to skew their immune system toward the IL-23/IL-17 pathway in periodontal lesions, which results in a predisposition to periodontal diseases. These studies help us to understand the complex immunological factors underlying susceptibility to periodontitis.