PKC-θ调控的Tregs/Teffs免疫平衡与氟中毒的关系研究

氟能对机体的免疫功能造成广泛且长期的损伤，但发病机理不清。有文献报道，氟可能会破坏调节T细胞（Tregs）/效应T细胞（Teffs）稳态，而Tregs/Teffs平衡在维持机体正常的免疫应答中发挥了重要的作用。有研究表明，在保持Tregs/Teffs平衡的动态过程中，蛋白激酶C-θ（PKC-θ）起到了核心作用。课题组前期研究也发现，染氟大鼠胸腺T淋巴细胞中p-PKC-θ表达降低，因此推测，氟可能是通过影响PKC-θ活性，使Tregs/Teffs稳态失衡，从而导致免疫功能损伤。本研究以PKC-θ为切入点，侧重低剂量氟的作用，拟通过现场流行病学调查和实验室研究，观察氟对PKC-θ调控的Tregs/Teffs免疫平衡及相关细胞因子的影响，探究氟致免疫功能损伤的特异性反应。以期从Tregs/Teffs免疫平衡的角度阐明氟致免疫功能损伤的机制，为寻找拮抗氟的有效药物作用分子靶点提供新思路。

Fluoride can lead to extensive and long-term immune function impairment, but the pathogenesis is unclear. It has been reported that fluoride may interfere the homeostasis of T cells (Tregs)/effector T cells (Teffs), and Tregs/Teffs balance plays an important role in maintaining normal immune response. It has been reported that protein kinase C-theta (PKC-θ) plays a core role in maintaining Tregs/Teffs balance. Our previous studies also found that the expression of p-PKC-θ decreased in thymic T lymphocytes of fluoride-exposed rats. Therefore, it is speculated that fluoride may cause imbalance of Tregs/Teffs by affecting the activity of PKC-θ, which may lead to the immune function impairment. In this study, we through epidemiological investigation and laboratory research, using PKC-θ as the starting point, focusing on the role of low-dose fluoride, to observe the effects of fluoride on Tregs/Teffs balance and related cytokines regulated by PKC-theta, to explore the specific response of immune function impairment induced by fluoride. In order to elucidate the mechanism of fluoride-induced immune impairment from the perspective of Tregs/Teffs immune balance, and provide new ideas for finding effective molecular targets of fluoride antagonists.