A study for the involvement of IL-22 in the pathogenesis of periodontal diseases

白细胞介素（IL）-22是由活化的辅助性T细胞产生的细胞因子之一，通过诱导角质形成细胞表达β-防御素，在宿主抵抗细菌感染中发挥重要作用。相反，由于IL-22主要由Th 17细胞产生，而Th 17细胞与细胞介导的组织损伤有关，因此IL-22也可能是参与疾病进展的可能细胞因子之一。为了评估IL-22在牙周病中的参与，我们评估了IL-22和IL-22受体在牙周病损中的表达水平以及牙周抗原特异性外周血T细胞IL-22的产生水平。首先，在每个牙龈活检样本中，评估病变部位及其对照部位中IL 22和IL 22 RA的基因表达。因此，我们可以检测到IL 22 RA的表达，几乎所有的牙龈活检样本，但IL 22的表达，可以检测到只有在少数样品。当比较病变部位和对照部位时，病变部位中IL 22 RA的基因表达水平显著高于对照部位。接下来，我们评估了来源于PBMC的对牙龈卟啉单胞菌的Ag 53特异的Th细胞克隆的IL-22产生。因此，我们可以在本研究中建立的许多T细胞克隆中检测到IL-22的产生。多数Th细胞克隆也具有产生IL-13和IFN-γ的能力，但未发现IL-22的产生与这些细胞因子的产生之间的相关性。根据这些发现，与外周血Th细胞中对牙周细菌抗原特异性应答的IL-22产生细胞的数量相比，牙周病变中产生IL-22的Th细胞的数量很少，这可能与牙周疾病的发病机制有关。

Interleukin (IL)-22, which is one of cytokines produced from activated helper T cells, plays an important role in the host defence against the bacterial infection by inducing the expression of β-defensin from keratinocytes. In contrast, since IL-22 is mostly produced from Th17 cells, which are implicated in the cell-mediated tissue damage, it is also likely that IL-22 is one of possible cytokines involved in the progression of the disease. In order to assess the involvement of IL-22 in periodontal diseases, we evaluated the expression level of IL-22 and IL-22 receptors in the periodontal lesions and the production level of IL-22 of peripheral blood T cells specific to periodontal antigens. Firstly, gene expression of IL22 and IL22RA were evaluated in the lesional sites and their control sites in each gingival biopsy sample. As a result, we could detect IL22RA expression in almost all gingival biopsy samples; however, the expression of IL22 could be detected in only a few samples. When compared between lesional sites and control sites, the gene expression levels of IL22RA in lesional sites were significantly higher than control sites. Next, we evaluated the IL-22 production of Th cell clones specific to Ag53 of P. gingivalis, which were derived from PBMCs. As a result, we could detect the IL-22 production in many T cell clones established in this study. Most of Th cell clones also had potential to produce IL-13 and IFN-γ, however, we could not find the correlations between IL-22 productivities and the production of these cytokines. From these findings, it might be implicated in the pathogenesis of the periodontal diseases that there are few numbers of Th cell producing IL-22 in periodontal lesions as compared with the numbers of IL-22 producing cells in the peripheral blood Th cells responding specific to the periodontal bacterial antigens.