Dai Bingying, Meng Meng, Chen Weilin, Zhou Junyu, Meng Qiming, Ding Liqing, Xie Shasha, Bao Ding, Li Xiaojing, Zhao Lijuan, Huang Ting, Lv Chunliu, Luo Hui, Liu Sijia, Zhu Honglin
The Department of Rheumatology and Immunology, Xiangya Hospital of Central South University, Changsha, People's Republic of China.
Department of Pathology, Xiangya Hospital, Changsha, People's Republic of China.
Int J Rheum Dis. 2025 May;28(5):e70250. doi: 10.1111/1756-185X.70250.
To investigate the effect of abatacept in the hypochlorous acid (HCLO)-induced fibrosis model and to analyze changes in immune cell fractions within the abatacept-treated early diffuse systemic sclerosis (SSc) cohort.
Fibrosis was induced in BALB/c mice by subcutaneous injection of HCLO, and abatacept was injected intraperitoneally on alternate days starting on day 28. After 6 weeks, we assessed the pathological changes, inflammation, myofibroblast activation, and the percentage of ICOS in CD3+ T cells. Potential pathways affected by abatacept were also investigated. Finally, we analyzed immune infiltration and multiple scores in early diffuse SSc patients and in the skin and lung tissues of the HCLO model after abatacept administration.
Abatacept significantly decreased the proportion of M2 macrophages in the abatacept-treated HCLO model and the inflammatory improver subset of SSc patients. Furthermore, abatacept reduced CD28 signaling, the inflammation-related pathway, and the ICOS expression on CD3+ T cells in HCLO mice. In the inflammatory subset of SSc patients and HCLO mice, microenvironmental and immune scores tended to decrease after abatacept treatment. Unexpectedly, abatacept had no effect on skin or lung collagen content in HCLO mice. The number of T cells and myofibroblasts was not reduced in the abatacept-treated HCLO group.
Although abatacept did not improve skin and lung fibrosis in the HCLO mice, it reduced the immune response signature and the proportion of M2 macrophages. These findings suggest that further research is needed to assess the therapeutic value of abatacept in SSc patients and preclinical mouse models.
研究阿巴西普在次氯酸（HCLO）诱导的纤维化模型中的作用，并分析阿巴西普治疗的早期弥漫性系统性硬化症（SSc）队列中免疫细胞分数的变化。
通过皮下注射HCLO在BALB/c小鼠中诱导纤维化，并从第28天开始隔天腹腔注射阿巴西普。6周后，我们评估了病理变化、炎症、肌成纤维细胞活化以及CD3+T细胞中诱导共刺激分子（ICOS）的百分比。还研究了受阿巴西普影响的潜在途径。最后，我们分析了阿巴西普给药后早期弥漫性SSc患者以及HCLO模型的皮肤和肺组织中的免疫浸润和多项评分。
阿巴西普显著降低了阿巴西普治疗的HCLO模型中M2巨噬细胞的比例以及SSc患者的炎症改善亚组中的M2巨噬细胞比例。此外，阿巴西普降低了HCLO小鼠中CD28信号传导、炎症相关途径以及CD3+T细胞上的ICOS表达。在SSc患者和HCLO小鼠的炎症亚组中，阿巴西普治疗后微环境和免疫评分趋于下降。出乎意料的是，阿巴西普对HCLO小鼠的皮肤或肺胶原蛋白含量没有影响。阿巴西普治疗的HCLO组中T细胞和成纤维细胞的数量没有减少。
尽管阿巴西普没有改善HCLO小鼠的皮肤和肺纤维化，但它降低了免疫反应特征和M2巨噬细胞的比例。这些发现表明，需要进一步研究来评估阿巴西普在SSc患者和临床前小鼠模型中的治疗价值。
