Characterization of Gingival Th1, Th2 and Th17 Cells in Murine Periodontitis Model

概要

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Cellular and molecular mechanisms of the immune system influencing oral bone metabolism remain to be elucidated. In this study, we characterize the mucosal cytokine production by CD4+ T cells in the inflamed gingiva of mice infected with Porphyromonas gingivalis (P. gingivalis). A murine periodontal disease model with alveolar bone loss showed significant levels of FimA-specific salivary secretory IgA and plasma IgG Ab responses. Further, IL-6 and TNF-α production was elevated when compared with sham-infected mice. The frequencies of Th1 (IFN-γ), Th2 (IL-4) and Th17 (IL-17) producing CD4+ T cells were also increased in P. gingivalis infected mice. Among these cytokines, a significantly higher frequency of IFN-γ producing CD4+ T cells was noted. The kinetics of intracellular cytokine analyses revealed a significantly increased frequency of IFN-γ-, IL-4- and IL-17-producing CD4+ T cells one day after infection. Further, the frequency of IFN-γ producing CD4+ T cells was maintained throughout the experimental period. Although IL-4 and IL-17 production was intact until 15 days after the infection, the numbers of CD4+ T cells producing these cytokines were reduced thereafter. These results indicate that Th1-type CD4+ T cells play distinct roles in the induction and regulation of periodontal disease when compared with Th2- and Th17-type cytokine-producing CD4+ T cells.