调节免疫平衡的低剂量白介素2在治疗骨质疏松症中的研究

Osteoporosis is a human health problem worldwide, but its pathogenesis and mechanism are not fully understood. Active T cell has a key role in the interaction between bone and immune system. Accumulated data have demonstrated quantitative or functional imbalance between T helper 17 (Th17) and regulatory T (Treg) cells in bone related disease, suggesting that Th17 and Treg involved in bone loss. Based on “Low-dose IL-2 appears to promote Treg-mediated immunologic tolerance and suppress Th17-mediated pathogenic responses” in previous studies, we propose low-dose IL-2 maybe inhibit osteoclast differentiation and bone loss on the Th17/Treg paradigm. Therefore, the purpose of this study is to determine the role of the Th17/Treg shift in estrogen deficiency-induced bone loss in mouse model and to elucidate the immunopharmacologic mechanism of low-dose IL-2 in preventing bone loss in this process by regulating Th17/Treg paradigm. These findings provide new insight into understanding of the molecular mechanisms underlying osteoporsosis.

骨质疏松是全球性的人类健康问题，但其病因、形成机制等尚未完成阐明。最新相关数据表明，体内调节性T细胞 （Regulatory T cells, Treg cells）和辅助性T细胞17（T helper17，Th17）失衡是促成骨流失的重要因素，根据前期研究中“低剂量Interleukin-2（IL-2）可诱导Treg细胞增殖，并负向调节Th17效应T细胞”的发现，提出低剂量IL-2可能通过恢复Th17/Treg稳态，来降低破骨细胞分化成熟，从而控制骨流失的设想。 因此，本课题拟以雌激素缺失诱导的骨质疏松小鼠为模型，基于恢复Th17/Treg稳态，利用生物学技术手段，探究低剂量IL-2在破骨细胞分化成熟及功能中的作用机制，阐明Th17/Treg平衡在骨质疏松症中的重要性，为研究骨质疏松的病因提供新的思路。

骨质疏松是全球性的人类健康问题，但其病因、形成机制等尚未完成阐明。最新相关数据 表明，体内调节性T细胞 (Regulatory T cells, Treg cells)和辅助性T细胞17(T helper1 7，Th17)失衡是促成骨流失的重要因素，根据前期研究中“低剂量Interleukin-2(IL-2)可 诱导Treg细胞增殖，并负向调节Th17效应T细胞”的发现，提出低剂量IL-2可能通过恢复Th17/ Treg稳态，来降低破骨细胞分化成熟，从而控制骨流失的设想。本项目重点研究了免疫调节剂低剂量 IL-2 在缓解和治疗原发性骨质疏松症发生发展中的作用，以恢复 Treg/Th17 稳态为切入点，从分子、细胞和动物水平，阐明低剂量IL-2能够通过抑制破骨细胞的分化和功能而显著缓解骨质疏松症的作用机制，进一步认识到免疫系统对于骨代谢平衡的重要性，发现新的治疗方法和作用靶点，以优化治疗方案，为研究骨质疏松的病因提供新的思路。