Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, USA.
Shanghai Stomatological Hospital, Fudan University, Shanghai, China.
Int Immunopharmacol. 2019 Apr;69:299-306. doi: 10.1016/j.intimp.2019.01.031. Epub 2019 Feb 10.
Pregnancy is a special period marked with complicated changes in various immune responses. Although pregnant women are prone to developing gingival inflammation, its immunological mechanism remains to be clarified. In a modified ligature-induced periodontal disease murine model, pregnant mice developed more severe alveolar bone loss. Using this model, we investigated the Treg responses during exacerbated periodontal disease in pregnant mice. We tested Treg-associated molecules in gingival tissues by quantitative real-time PCR and found decreased gingival expression of Foxp3, TGFβ, CTLA-4, and CD28 in pregnant mice after periodontal disease induction. We further confirmed that lower number of Treg cells were present in the cervical lymph nodes of pregnant periodontitis mice. Treg cells from the cervical lymph nodes of ligated pregnant mice and non-pregnant mice were tested for their suppressive function in vitro. We manifested that Treg suppressive function was also down-regulated in the pregnant mice. Additionally, we demonstrated that more inflammatory Th17 cells were present in the cervical lymph nodes of ligated pregnant mice. Therefore, impaired Treg development and function, together with upregulated Th17 response, may contribute to the exacerbated periodontal disease during pregnancy.
妊娠是一个特殊的时期,其各种免疫反应发生复杂变化。尽管孕妇易发生牙龈炎症,但其免疫学机制仍不清楚。在改良的结扎诱导牙周病小鼠模型中,妊娠小鼠出现更严重的牙槽骨丧失。使用该模型,我们研究了妊娠小鼠牙周病加重期间的 Treg 反应。我们通过定量实时 PCR 检测了牙龈组织中的 Treg 相关分子,发现牙周病诱导后妊娠小鼠的牙龈组织中 Foxp3、TGFβ、CTLA-4 和 CD28 的表达降低。我们进一步证实,妊娠牙周炎小鼠颈淋巴结中 Treg 细胞数量减少。我们测试了结扎妊娠和非妊娠小鼠颈淋巴结中的 Treg 细胞的体外抑制功能。结果表明,妊娠小鼠的 Treg 抑制功能也下调。此外,我们还证明,结扎妊娠小鼠颈淋巴结中存在更多的炎性 Th17 细胞。因此,Treg 的发育和功能受损,以及 Th17 反应上调,可能导致妊娠期间牙周病加重。