Single-cell transcriptome profile of mouse skin undergoing antigen-driven allergic inflammation recapitulates findings in atopic dermatitis skin lesions.
Single-cell transcriptome profile of mouse skin undergoing antigen-driven allergic inflammation recapitulates findings in atopic dermatitis skin lesions.
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DOI：
10.1016/j.jaci.2022.03.002
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发表时间：
2022-08
影响因子：
14.2
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
--
作者：
Leyva-Castillo, Juan Manuel;Sun, Liang;Wu, Shih-Ying;Rockowitz, Shira;Sliz, Piotr;Geha, Raif S.
小鼠经皮（EC）抗原致敏引起的过敏性皮肤炎症与人类特应性皮炎（AD）具有相同的特征。表征经历抗原驱动的过敏性炎症的小鼠皮肤中单细胞的基因表达，并将结果与 AD 皮肤损伤的结果进行比较。通过将卵清蛋白 (OVA) 或盐水涂在剥离皮肤的胶带上，使小鼠 EC 致敏。 12 天后，对皮肤细胞进行单细胞 RNA 测序 (scRNA-Seq)。进行流式细胞术分析以验证结果。 scRNA-Seq 在 EC 致敏小鼠皮肤中鉴定出 7 个非造血细胞和 6 个造血细胞亚群。 OVA致敏导致皮肤中T细胞、树突状细胞(DC)、巨噬细胞、肥大细胞/嗜碱性粒细胞、成纤维细胞和肌细胞细胞簇的扩增，并导致CD4+ T细胞和肥大/细胞嗜碱性粒细胞中Th2细胞因子基因表达的上调。 OVA 致敏皮肤中差异表达的基因包括对 DC 和巨噬细胞炎症、成纤维细胞中胶原沉积和白细胞迁移、内皮细胞趋化性以及 KC 中皮肤屏障完整性和分化很重要的基因，这些发现概括了 AD 皮肤病变中的发现。出乎意料的是，肥大/细胞嗜碱性粒细胞，而不是T细胞，是OVA致敏小鼠皮肤中Il4和ll13的主要来源。此外，我们的结果表明成纤维细胞和内皮细胞中的新途径可能导致过敏性皮肤炎症。接受抗原驱动的小鼠皮肤中单细胞的基因表达谱与 AD 皮肤损伤中的单细胞有许多共同特征，并揭示了可能与过敏性皮肤炎症有关的新途径。单细胞水平的基因表达分析揭示了小鼠抗原驱动的过敏性皮肤炎症与 AD 皮肤病变之间的相似性，并揭示了可能导致过敏性皮肤炎症的新途径。
Allergic skin inflammation elicited in mice by epicutaneous (EC) sensitization with antigen shares characteristics with human atopic dermatitis (AD). To characterize gene expression by single cells in mouse skin undergoing antigen-driven allergic inflammation and compare the results with findings in AD skin lesions. Mice were EC sensitized by application of ovalbumin (OVA) or saline to tape stripped skin. Single-cell RNA-Seq (scRNA-Seq) was performed on skin cells twelve days later. Flow cytometry analysis was performed to validate results. scRNA-Seq identified seven nonhematopoietic and six hematopoietic cell subsets in EC sensitized mouse skin. OVA sensitization resulted in the expansion in the skin of T cells, dendritic cells (DCs), macrophages, mast cell/basophils, fibroblasts and myocytes cell clusters, and in upregulation of Th2 cytokine gene expression in CD4+ T cells and mast/cell basophils. Genes differentially expressed in OVA sensitized skin included genes important for inflammation in DCs and macrophages, collagen deposition and leukocyte migration in fibroblasts, chemotaxis in endothelial cells and skin barrier integrity and differentiation in KCs, findings that recapitulate those in AD skin lesions. Unexpectedly, mast/cell basophils, rather than T cells, were the major source of Il4 and ll13 in OVA sensitized mouse skin. In addition, our results suggest novel pathways in fibroblast and endothelial cells that may contribute to allergic skin inflammation. The gene expression profile of single cells in mouse skin undergoing antigen-driven shares many features with that in AD skin lesions, and unveils novel pathways that may be involved in allergic skin inflammation. Analysis of gene expression at the single cell level reveals similarities between antigen-driven allergic skin inflammation in mice and AD skin lesions and unveils novel pathways that may contribute to allergic skin inflammation.
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影响因子：
12.3
作者：
Ghahramani, Arsham;Donati, Giacomo;Watt, Fiona M.
通讯作者：
Watt, Fiona M.
影响因子：
64.5
作者：
Claudia Salzer, Marion;Lafzi, Atefeh;Aznar Benitah, Salvador
通讯作者：
Aznar Benitah, Salvador
DOI：
10.1155/2012/718725
发表时间：
2012
期刊：
Journal of allergy
影响因子：
--
作者：
Bernard FX;Morel F;Camus M;Pedretti N;Barrault C;Garnier J;Lecron JC
通讯作者：
Lecron JC
影响因子：
6.5
作者：
Danso, Mogbekeloluwa O.;van Drongelen, Vincent;Bouwstra, Joke A.
通讯作者：
Bouwstra, Joke A.
DOI：
10.1016/j.jaci.2017.01.011
发表时间：
2017-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brunner PM;Guttman-Yassky E;Leung DY
通讯作者：
Leung DY