Developmental cell programs are co-opted in inflammatory skin disease.

Developmental cell programs are co-opted in inflammatory skin disease.
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DOI:
10.1126/science.aba6500
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发表时间:
2021-01-22
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Haniffa M
Haniffa M
中科院分区:
其他
文献类型:
--
作者:
Reynolds G;Vegh P;Fletcher J;Poyner EFM;Stephenson E;Goh I;Botting RA;Huang N;Olabi B;Dubois A;Dixon D;Green K;Maunder D;Engelbert J;Efremova M;Polański K;Jardine L;Jones C;Ness T;Horsfall D;McGrath J;Carey C;Popescu DM;Webb S;Wang XN;Sayer B;Park JE;Negri VA;Belokhvostova D;Lynch MD;McDonald D;Filby A;Hagai T;Meyer KB;Husain A;Coxhead J;Vento-Tormo R;Behjati S;Lisgo S;Villani AC;Bacardit J;Jones PH;O'Toole EA;Ogg GS;Rajan N;Reynolds NJ;Teichmann SA;Watt FM;Haniffa M

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皮肤通过在胚胎发育早期建立的复杂细胞网络提供生物物理和免疫保护。我们分析了来自发育中的胎儿和成人健康皮肤以及患有特应性皮炎和牛皮癣的成人皮肤的500,000多个单细胞的转录本。我们利用这些数据集来比较发育、动态平衡和疾病的细胞状态。我们的分析显示,在特应性皮炎和牛皮癣的前三个月,皮肤中天然免疫细胞的丰富和疾病相关淋巴细胞的克隆性扩张。我们发现并在原位验证了特应性皮炎和牛皮癣皮损皮肤中产前血管内皮细胞和巨噬细胞程序的重新出现。这些数据说明了皮肤免疫的动态,并为针对炎症性皮肤病的病理发育程序提供了机会。
The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of over 500,000 single cells from developing fetal and adult healthy human skin, and from adult skin with atopic dermatitis and psoriasis. We leveraged these data sets to compare cell states across development, homeostasis and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a re-emergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
Langerhans细胞(LC)增殖介导了新生儿发育,体内平衡和与表皮LC网络的炎症相关扩张。
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