徐州医科大学刘强团队在研究中取得进展。他们发现FPR2/ALX刺激调节小胶质细胞和自然杀伤细胞以限制自身免疫性星形胶质细胞病。这一研究成果发表在2026年3月10日出版的国际学术期刊《中国药理学报》上。

通过AQP4-IgG和补体介导的细胞毒性诱导的自身免疫性星形细胞病的单主题模型，研究人员发现用小分子激动剂Quin-C1刺激FPR2/ALX可减少脑损伤体积、星形细胞损失和脱髓鞘。这伴随着小胶质细胞抗炎活性增强和大脑淋巴细胞浸润减少。FPR2/ALX刺激也导致自身免疫性星形细胞病小鼠中SYK和AKT磷酸化升高。

值得注意的是，在患有自身免疫性星形细胞病的小鼠中，以CSF1R抑制剂PLX5622为主题的小胶质细胞耗尽或以抗NK1.1单克隆抗体为主题的自然杀伤（NK）细胞耗尽后，FPR2/ALX刺激的益处减弱。此外，在接受SYK抑制剂R406的自身免疫性星形细胞病小鼠中，FPR2/ALX刺激的保护作用减弱。总的来说，他们的研究结果表明，FPR2/ALX刺激可能是一种有希望的治疗策略，通过调节小胶质细胞和NK细胞来减轻自身免疫性星形细胞病的有害神经炎症。

据悉，自身抗体和补体介导的细胞毒性可介导自身免疫性星形细胞病，导致中枢神经系统炎症性脱髓鞘。甲酰基肽受体2 （FPR2/ALX）控制免疫应答的激活和传播。然而，FPR2/ALX在神经炎症中的确切作用以及FPR2/ALX刺激对自身免疫性星形细胞病的影响尚不清楚。

附：英文原文

Title: FPR2/ALX stimulation modulates microglia and natural killer cells to restrict autoimmune astrocytopathy

Author: Qi, Cai-yun, Chen, Li-xiang, Fu, Yi-wei, Wang, Peng-xu, Zhang, Wei, Han, Ya-li, Xu, Tong-xiao, Li, Yuan, Wang, Xiao-zhen, Cui, Gui-yun, Chen, Hao, Wang, Ming-Wei, Liu, Qiang

Issue&Volume: 2026-03-10

Abstract: Autoantibody- and complement-mediated cytotoxicity can cause autoimmune astrocytopathy that leads to CNS inflammatory demyelination. Formyl peptide receptor 2 (FPR2/ALX) governs the activation and propagation of immune response. However, the precise role of FPR2/ALX in neuroinflammation and the effect of FPR2/ALX stimulation on autoimmune astrocytopathy are poorly understood. Using a mouse model of autoimmune astrocytopathy induced by AQP4-IgG- and complement-mediated cytotoxicity, we found that the stimulation of FPR2/ALX with the small-molecule agonist Quin-C1 led to reduced brain lesion volume, astrocyte loss and demyelination. This was accompanied by enhanced anti-inflammatory activity of microglia and reduced infiltration of lymphocytes in the brain. FPR2/ALX stimulation also led to increased phosphorylation of SYK and AKT in mice with autoimmune astrocytopathy. Notably, the benefits of FPR2/ALX stimulation were attenuated in mice with autoimmune astrocytopathy after microglial depletion using the CSF1R inhibitor PLX5622 or natural killer (NK) cell depletion using an anti-NK1.1 monoclonal antibody. Additionally, the protective effects of FPR2/ALX stimulation were diminished in mice with autoimmune astrocytopathy that received the SYK inhibitor R406. Collectively, our findings demonstrate that FPR2/ALX stimulation may represent a promising therapeutic strategy to attenuate detrimental neuroinflammation in autoimmune astrocytopathy by modulating microglia and NK cells.

DOI: 10.1038/s41401-026-01778-w

Source: https://www.nature.com/articles/s41401-026-01778-w