Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.
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DOI:
10.1016/j.xcrm.2023.101373
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发表时间:
2024-01-16
影响因子:
14.3
通讯作者:
Grimson, Andrew
Grimson, Andrew
中科院分区:
医学1区
文献类型:
--
作者:
Vu, Luyen Tien;Ahmed, Faraz;Zhu, Hongya;Iu, David Shing Huk;Fogarty, Elizabeth A.;Kwak, Yeonui;Chen, Weizhong;Franconi, Carl J.;Munn, Paul R.;Tate, Ann E.;Levine, Susan M.;Stevens, Jared;Mao, Xiangling;Shungu, Dikoma C.;Moore, Geoffrey E.;Keller, Betsy A.;Hanson, Maureen R.;Grenier, Jennifer K.;Grimson, Andrew

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肌痛性脑脊髓炎/慢性疲劳综合征(ME/CFS)是一种严重且知之甚少的疾病。为了了解ME/CFS的免疫失调,我们使用单细胞RNA测序(scRNA-seq)来检测患者和对照队列中的免疫细胞。劳后不适(PEM)是剧烈运动后症状的加剧,是ME/CFS的特征症状。为了检测与PEM一致的变化,我们在练习后对相同的队列应用了scRNA-seq。在基线水平,ME/CFS患者表现出典型的单核细胞失调,提示不适当的分化和向组织的迁移。我们在患者中识别出患病的单核细胞和更正常的单核细胞,患病细胞的比例与疾病的严重程度相关。比较基线和运动后挑战时的转录组,我们发现了表明患者血小板异常激活的模式,免疫系统其他方面的变化很小。综上所述,这些数据确定了患者基线时存在的免疫缺陷和额外的一层血小板调节失调。用scRNA-seq分析ME/CFS免疫系统在激发前和激发后的状态,单核细胞调节异常明显,且与疾病严重程度相关的调节失调,血小板也调节失调,但这种调节失调在激发后得到解决。检测ME/CFS患者免疫细胞基因表达的变化。作者强调单核细胞失调是ME/CFS免疫系统的一个显著特征,这种失调与疾病的严重程度相关。
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets. The ME/CFS immune system is profiled by scRNA-seq at baseline and after provocation Monocyte dysregulation is prominent and dysregulation correlates with disease severity Platelets are also dysregulated, but this dysregulation resolves after provocation Vu et al. examine changes in gene expression in immune cells of ME/CFS patients. The authors highlight monocyte dysregulation as a prominent feature of the immune system in ME/CFS, and this dysregulation correlates with disease severity.
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