Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells.
Single cell transcriptional zonation of human psoriasis skin identifies an alternative immunoregulatory axis conducted by skin resident cells.
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DOI：
10.1038/s41419-021-03724-6
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发表时间：
2021-05-06
影响因子：
9
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Gao Y;Yao X;Zhai Y;Li L;Li H;Sun X;Yu P;Xue T;Li Y;Hu Y
牛皮癣是成人最常见的皮肤病。目前的实验和临床证据表明，浸润的免疫细胞可以靶向局部皮肤细胞，从而诱导银屑病表型。然而，最近的研究表明，存在一个潜在的反馈信号回路，从当地居民皮肤细胞浸润免疫细胞。在这里，我们在单细胞转录水平上解构了健康供体和寻常型银屑病患者的全层人类皮肤，并进一步构建了一个神经网络分类器，以评估小鼠和人类之间皮肤细胞类型的进化保守性。最后，我们系统地评估了健康皮肤和银屑病皮肤中每种细胞类型的内在和细胞间分子改变。与银屑病易感基因位点、基于细胞类型的差异表达和配体-受体通讯的交叉检查显示，银屑病皮肤细胞包括间充质和表皮细胞类型，其特异性地携带银屑病易感基因位点的靶基因，强烈地诱发主要组织相容性复合体（MHC）基因的表达，上调干扰素（INF），肿瘤坏死因子（TNF）信号传导和增加的细胞因子基因表达主要针对银屑病中邻近的树突状细胞。通过对银屑病患者活检组织的全面探索和病理观察，揭示了从皮肤局部驻留细胞到免疫细胞的免疫调节轴，为银屑病的治疗提供了新的思路。此外，我们发布了一个用户友好的网站，展示健康和银屑病人类皮肤之间的每种细胞类型的转录变化。
Psoriasis is the most common skin disease in adults. Current experimental and clinical evidences suggested the infiltrating immune cells could target local skin cells and thus induce psoriatic phenotype. However, recent studies indicated the existence of a potential feedback signaling loop from local resident skin cells to infiltrating immune cells. Here, we deconstructed the full-thickness human skins of both healthy donors and patients with psoriasis vulgaris at single cell transcriptional level, and further built a neural-network classifier to evaluate the evolutional conservation of skin cell types between mouse and human. Last, we systematically evaluated the intrinsic and intercellular molecular alterations of each cell type between healthy and psoriatic skin. Cross-checking with psoriasis susceptibility gene loci, cell-type based differential expression, and ligand-receptor communication revealed that the resident psoriatic skin cells including mesenchymal and epidermis cell types, which specifically harbored the target genes of psoriasis susceptibility loci, intensively evoked the expression of major histocompatibility complex (MHC) genes, upregulated interferon (INF), tumor necrosis factor (TNF) signalling and increased cytokine gene expression for primarily aiming the neighboring dendritic cells in psoriasis. The comprehensive exploration and pathological observation of psoriasis patient biopsies proposed an uncovered immunoregulatory axis from skin local resident cells to immune cells, thus provided a novel insight for psoriasis treatment. In addition, we published a user-friendly website to exhibit the transcriptional change of each cell type between healthy and psoriatic human skin.
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影响因子：
23.9
作者：
Joost, Simon;Annusver, Karl;Kasper, Maria
通讯作者：
Kasper, Maria
影响因子：
64.8
作者：
Capper D;Jones DTW;Sill M;Hovestadt V;Schrimpf D;Sturm D;Koelsche C;Sahm F;Chavez L;Reuss DE;Kratz A;Wefers AK;Huang K;Pajtler KW;Schweizer L;Stichel D;Olar A;Engel NW;Lindenberg K;Harter PN;Braczynski AK;Plate KH;Dohmen H;Garvalov BK;Coras R;Hölsken A;Hewer E;Bewerunge-Hudler M;Schick M;Fischer R;Beschorner R;Schittenhelm J;Staszewski O;Wani K;Varlet P;Pages M;Temming P;Lohmann D;Selt F;Witt H;Milde T;Witt O;Aronica E;Giangaspero F;Rushing E;Scheurlen W;Geisenberger C;Rodriguez FJ;Becker A;Preusser M;Haberler C;Bjerkvig R;Cryan J;Farrell M;Deckert M;Hench J;Frank S;Serrano J;Kannan K;Tsirigos A;Brück W;Hofer S;Brehmer S;Seiz-Rosenhagen M;Hänggi D;Hans V;Rozsnoki S;Hansford JR;Kohlhof P;Kristensen BW;Lechner M;Lopes B;Mawrin C;Ketter R;Kulozik A;Khatib Z;Heppner F;Koch A;Jouvet A;Keohane C;Mühleisen H;Mueller W;Pohl U;Prinz M;Benner A;Zapatka M;Gottardo NG;Driever PH;Kramm CM;Müller HL;Rutkowski S;von Hoff K;Frühwald MC;Gnekow A;Fleischhack G;Tippelt S;Calaminus G;Monoranu CM;Perry A;Jones C;Jacques TS;Radlwimmer B;Gessi M;Pietsch T;Schramm J;Schackert G;Westphal M;Reifenberger G;Wesseling P;Weller M;Collins VP;Blümcke I;Bendszus M;Debus J;Huang A;Jabado N;Northcott PA;Paulus W;Gajjar A;Robinson GW;Taylor MD;Jaunmuktane Z;Ryzhova M;Platten M;Unterberg A;Wick W;Karajannis MA;Mittelbronn M;Acker T;Hartmann C;Aldape K;Schüller U;Buslei R;Lichter P;Kool M;Herold-Mende C;Ellison DW;Hasselblatt M;Snuderl M;Brandner S;Korshunov A;von Deimling A;Pfister SM
通讯作者：
Pfister SM
影响因子：
64.8
作者：
Hovestadt, Volker;Smith, Kyle S.;Northcott, Paul A.
通讯作者：
Northcott, Paul A.
DOI：
10.1038/nrdp.2016.82
发表时间：
2016-11-24
期刊：
Nature reviews. Disease primers
影响因子：
--
作者：
Greb, Jacqueline E;Goldminz, Ari M;Gottlieb, Alice B
通讯作者：
Gottlieb, Alice B
影响因子：
3.6
作者：
Bray, Eric R.;Cheret, Jeremy;Paus, Ralf
通讯作者：
Paus, Ralf