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干扰素激活在骨髓长寿血细胞中的系统性红血狼

Diana F Alzamareh¹, Nida Meednu¹, Neha Nandedkar-Kulkarni¹

¹Division of Allergy, Immunology and Rheumatology, University of Rochester Medical Center, Rochester, NY, United States.

Frontiers in immunology

|January 27, 2025

概括

骨髓中的长寿命血细胞 (LLPC) 在全身性红斑狼 (SLE) 中显示干扰素激活. 针对这些自身反应性LLPC可以为SLE等自身免疫性疾病提供新的治疗方法.

科学领域:

免疫学免疫学免疫学
这是一种自身免疫力.
细胞生物学细胞生物学

背景情况:

长寿命血细胞 (LLPC) 对免疫非常重要,但可以通过产生自我反应抗体来驱动自身免疫性疾病,如全身性红斑狼 (SLE).
消除自身反应性LLPC是抗体驱动的自身免疫疾病的潜在治疗策略,但LLPC仍然是一个困难的目标.
了解LLPC在不同身体部位的特征是开发有效治疗的关键.

研究的目的:

为了比较SLE患者和健康捐赠者的骨髓 (BM) 和外周血液 (PBL) 中的血细胞 (PC) 种群.
调查干扰素 (IFN) 信号和激活在SLE患者的BM PC中的作用.
评估针对SLE的LLPC的治疗潜力.

主要方法:

对CD138+和CD138-PC种群的比较分析,包括假定的LLPC (CD19-CD138+CD38+),在SLE和HD的BM和PBL中.
转录组分析以确定B细胞和PC中的基因表达模式,特别是IFN签名.
实验室研究评估STAT1酸化对I型IFN的反应和结合于anifrolumab,以及使用verdinexor进行PC存活测定.

主要成果:

在SLE和HD的BM中观察到PC子集的类似分布,包括假定的LLPC.
在过渡性B细胞中检测到IFN基因特征,令人惊的是,在SLE患者的BM衍生PC中检测到IFN基因特征.
来自SLE患者的BM PC显示出IFN激活,STAT1酸化和与阿尼弗罗卢马布结合的证据,尽管比循环中的B细胞更小. 抗核自身抗体 (ANA) 存在于SLE患者的BM超和PBL血清中.

结论:

在SLE患者的骨髓PC中显示出I型干扰素激活的证据.
这些发现凸显了BM PC在SLE病变发生过程中的潜在参与.
向IFN激活的BMPC可能是SLE和其他自身免疫疾病的新疗法.

关键词:

B细胞是B细胞的组成部分.这样,我们就有了anifrolumab.骨髓骨髓骨髓骨髓骨髓干扰子干扰子干扰子狼 (SLE) 是一种疾病.血细胞 (PC) 是一种过渡的 B 细胞.绿色的绿色的xorinexor

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