Lupus Susceptibility Loci Predispose Mice to Clonal Lymphocytic Responses and Myeloid Expansion.
Lupus Susceptibility Loci Predispose Mice to Clonal Lymphocytic Responses and Myeloid Expansion.
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红斑狼疮易感位点使小鼠易受克隆淋巴细胞反应和骨髓扩增的影响。
DOI：
10.4049/jimmunol.2200098
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发表时间：
2022-05-15
期刊：
影响因子：
--
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中科院分区：
文献类型：
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作者：
狼疮易感性是由许多遗传基因座的联合作用引起的，但由于自身免疫免疫应答的细胞异质性大，这些基因座对疾病发病机制的贡献一直难以研究。我们进行了单细胞RNA，B细胞受体（BCR），T细胞受体（TCR）测序的小鼠脾细胞与多个多态性狼疮易感基因座。我们不仅观察到淋巴细胞和骨髓扩增，而且还表征了亚群频率和基因表达的变化，例如减少的CD 8和边缘区B细胞和增加的Fcr 15和Cd 51表达巨噬细胞。克隆型分析揭示了B和CD 4克隆的扩增，并且来自狼疮易感小鼠的TCR库可通过算法特异性预测和无监督机器学习分类来区分。髓系差异基因表达、代谢和配体-受体相互作用的改变与抗原呈递减少相关。该数据集为狼疮自发模型的病理生理学提供了新的机制见解，突出了自身抗体介导疾病的潜在治疗靶点。
Lupus susceptibility results from the combined effects of numerous genetic loci, but the contribution of these loci to disease pathogenesis has been difficult to study due to the large cellular heterogeneity of the autoimmune immune response. We performed single cell RNA, B cell receptor (BCR), and T cell receptor (TCR) sequencing of splenocytes from mice with multiple polymorphic lupus susceptibility loci. We not only observed lymphocyte and myeloid expansion, but also characterized changes in subset frequencies and gene expression, such as decreased CD8 and marginal zone B cells and increased Fcrl5 and Cd5l expressing macrophages. Clonotypic analyses revealed expansion of B and CD4 clones, and TCR repertoires from lupus prone mice were distinguishable by algorithmic specificity prediction and unsupervised machine learning classification. Myeloid differential gene expression, metabolism, and altered ligand-receptor interaction were associated with decreased antigen presentation. This dataset provides novel mechanistic insight into the pathophysiology of a spontaneous model of lupus, highlighting potential therapeutic targets for autoantibody mediated disease.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
16.6
作者：
Buang N;Tapeng L;Gray V;Sardini A;Whilding C;Lightstone L;Cairns TD;Pickering MC;Behmoaras J;Ling GS;Botto M
通讯作者：
Botto M
DOI：
10.1002/art.40038
发表时间：
2017-05
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Comte D;Karampetsou MP;Yoshida N;Kis-Toth K;Kyttaris VC;Tsokos GC
通讯作者：
Tsokos GC
影响因子：
64.5
作者：
Birnbaum ME;Mendoza JL;Sethi DK;Dong S;Glanville J;Dobbins J;Ozkan E;Davis MM;Wucherpfennig KW;Garcia KC
通讯作者：
Garcia KC
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium