The role of Sp140 revealed in IgE and mast cell responses in Collaborative Cross mice.

The role of Sp140 revealed in IgE and mast cell responses in Collaborative Cross mice.
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DOI:
10.1172/jci.insight.146572
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发表时间:
2021-06-22
期刊:
影响因子:
8
通讯作者:
Galli SJ
Galli SJ
中科院分区:
医学1区
文献类型:
--
作者:
Matsushita K;Li X;Nakamura Y;Dong D;Mukai K;Tsai M;Montgomery SB;Galli SJ

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小鼠IgE和肥大细胞(MC)功能的研究主要是利用近交系进行的。在这里,我们(a)确定了遗传背景对小鼠IgE和MC表型的影响,(b)确定了研究IgE和MC功能的各种菌株的适用性,(c)开始研究参与这些功能的潜在新基因。我们筛选了47株协作交叉(CC)菌株,以及C57BL/6J和BALB/cJ小鼠,检测被动皮肤过敏反应(PCA)的强度和对肠道寄生虫委内瑞拉圆线虫(s.v.)的反应。CC小鼠在PCA强度和S.v.反应上表现出多样性。在实验菌株中,C57BL/6J和CC027小鼠分别表现出中等和独特的强MC活性。对CC027小鼠培养的脑源性MCs (BMCMCs)进行了数量性状位点分析和RNA测序,结果表明Sp140是MCs激活的候选基因。在BMCMCs中,sirna介导的Sp140敲低可减少ige依赖性组胺释放和细胞因子产生。我们的研究结果表明,不同CC菌株体内的IgE和MC活性以及对S.v的反应存在显著差异。C57BL/6J和CC027是研究MC函数的有用模型。此外,我们发现Sp140是一个促进ige依赖性MC激活的基因。
Mouse IgE and mast cell (MC) functions have been studied primarily using inbred strains. Here, we (a) identified effects of genetic background on mouse IgE and MC phenotypes, (b) defined the suitability of various strains for studying IgE and MC functions, and (c) began to study potentially novel genes involved in such functions. We screened 47 Collaborative Cross (CC) strains, as well as C57BL/6J and BALB/cJ mice, for strength of passive cutaneous anaphylaxis (PCA) and responses to the intestinal parasite Strongyloides venezuelensis (S.v.). CC mice exhibited a diversity in PCA strength and S.v. responses. Among strains tested, C57BL/6J and CC027 mice showed, respectively, moderate and uniquely potent MC activity. Quantitative trait locus analysis and RNA sequencing of BM-derived cultured MCs (BMCMCs) from CC027 mice suggested Sp140 as a candidate gene for MC activation. siRNA-mediated knock-down of Sp140 in BMCMCs decreased IgE-dependent histamine release and cytokine production. Our results demonstrated marked variations in IgE and MC activity in vivo, and in responses to S.v., across CC strains. C57BL/6J and CC027 represent useful models for studying MC functions. Additionally, we identified Sp140 as a gene that contributes to IgE-dependent MC activation.
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