Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry

Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
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DOI:
10.7554/elife.48051
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发表时间:
2019-08-01
期刊:
影响因子:
7.7
通讯作者:
Gommerman, Jennifer L.
Gommerman, Jennifer L.
中科院分区:
生物学1区
文献类型:
--
作者:
Ramaglia, Valeria;Sheikh-Mohamed, Salma;Gommerman, Jennifer L.

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多发性硬化症(MS)的特征是脑和脊髓中的脱髓鞘和炎性病变,其在细胞含量方面高度可变。在这里,我们使用成像质谱细胞术(IMC),使15+蛋白质分期MS病变内的同时成像。为了测试IMC区分不同类型病变的潜力,我们选择了一个在那他珠单抗停药后具有严重反弹MS疾病活动的病例。通过采集后分析管道,我们能够:(1)从驻留的小胶质细胞库中区分脱髓鞘巨噬细胞;(2)确定哪种类型的淋巴细胞最接近血管;(3)识别T和B细胞的多个子集,以及(4)确定T细胞表型维斯病变类型和位置的动力学。我们建议,IMC将使单细胞表型的综合分析,其功能状态和细胞间的相互作用与病变形态和脱髓鞘活动在MS患者。
Multiple sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord that are highly variable in terms of cellular content. Here, we used imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within staged MS lesions. To test the potential for IMC to discriminate between different types of lesions, we selected a case with severe rebound MS disease activity after natalizumab cessation. With post-acquisition analysis pipelines we were able to: (1) Discriminate demyelinating macrophages from the resident microglial pool; (2) Determine which types of lymphocytes reside closest to blood vessels; (3) Identify multiple subsets of T and B cells, and (4) Ascertain dynamics of T cell phenotypes vis-a-vis lesion type and location. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in MS patients.