Structural cells are key regulators of organ-specific immune responses.
Structural cells are key regulators of organ-specific immune responses.
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结构细胞是器官特异性免疫反应的关键调节剂。
DOI：
10.1038/s41586-020-2424-4
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发表时间：
2020-07
期刊：
影响因子：
64.8
通讯作者：
Bock C
中科院分区：
文献类型：
--
作者：
Krausgruber T;Fortelny N;Fife-Gernedl V;Senekowitsch M;Schuster LC;Lercher A;Nemc A;Schmidl C;Rendeiro AF;Bergthaler A;Bock C
哺乳动物的免疫系统实施了一套非常有效的机制来对抗病原体。其主要成分是造血免疫细胞，包括控制先天免疫的髓系细胞和构成适应性免疫的淋巴细胞。然而，免疫功能并不是造血细胞所独有的，许多其他细胞类型也显示出病原体防御的基本机制。为了促进我们对造血系统外免疫学的理解，在这里，我们系统地研究了三种主要类型的结构细胞中免疫基因的调节：上皮细胞、内皮细胞和成纤维细胞。我们使用细胞表型分析、转录组测序、染色质可及性分析和表观基因组作图来表征小鼠12个器官中的这些细胞类型。这一全面的数据集揭示了结构细胞中复杂的免疫基因活性和调控。观察到的模式是高度器官特异性的，似乎调节结构细胞和造血免疫细胞之间的广泛相互作用。此外，我们确定了一个表观遗传编码的免疫潜力的结构细胞下的组织稳态，这是触发系统性病毒感染。这项研究强调了非造血结构细胞中免疫基因活性的普遍性和器官特异性复杂性，并提供了调节小鼠结构细胞的表观遗传和转录网络的高分辨率，多组学图谱。
The mammalian immune system implements a remarkably effective set of mechanisms for fighting pathogens. Its main components are hematopoietic immune cells, including myeloid cells that control innate immunity and lymphoid cells that constitute adaptive immunity. However, immune functions are not unique to hematopoietic cells, and many other cell types display basic mechanisms of pathogen defence. To advance our understanding of immunology outside the haematopoietic system, here we systematically investigate the regulation of immune genes in the three major types of structural cells: epithelium, endothelium, and fibroblasts. We characterize these cell types across twelve organs in mice, using cellular phenotyping, transcriptome sequencing, chromatin-accessibility profiling, and epigenome mapping. This comprehensive dataset revealed complex immune gene activity and regulation in structural cells. The observed patterns were highly organ-specific and seem to modulate the extensive interactions between structural cells and haematopoietic immune cells. Moreover, we identified an epigenetically encoded immune potential in structural cells under tissue homeostasis, which was triggered in response to systemic viral infection. This study highlights the prevalence and organ-specific complexity of immune gene activity in non-haematopoietic structural cells, and it provides a high-resolution, multi-omics atlas of the epigenetic and transcriptional networks that regulate structural cells in the mouse.
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影响因子：
16.6
作者：
Krausgruber T;Schiering C;Adelmann K;Harrison OJ;Chomka A;Pearson C;Ahern PP;Shale M;Oukka M;Powrie F
通讯作者：
Powrie F
影响因子：
64.5
作者：
Kinchen J;Chen HH;Parikh K;Antanaviciute A;Jagielowicz M;Fawkner-Corbett D;Ashley N;Cubitt L;Mellado-Gomez E;Attar M;Sharma E;Wills Q;Bowden R;Richter FC;Ahern D;Puri KD;Henault J;Gervais F;Koohy H;Simmons A
通讯作者：
Simmons A
影响因子：
4.4
作者：
Kouadjo KE;Nishida Y;Cadrin-Girard JF;Yoshioka M;St-Amand J
通讯作者：
St-Amand J
影响因子：
30.8
作者：
Corces, M. Ryan;Buenrostro, Jason D.;Wu, Beijing;Greenside, Peyton G.;Chan, Steven M.;Koenig, Julie L.;Snyder, Michael P.;Pritchard, Jonathan K.;Kundaje, Anshul;Gkeenleaf, William J.;Majeti, Ravindra;Chang, Howard Y.
通讯作者：
Chang, Howard Y.
影响因子：
64.8
作者：
Montoro DT;Haber AL;Biton M;Vinarsky V;Lin B;Birket SE;Yuan F;Chen S;Leung HM;Villoria J;Rogel N;Burgin G;Tsankov AM;Waghray A;Slyper M;Waldman J;Nguyen L;Dionne D;Rozenblatt-Rosen O;Tata PR;Mou H;Shivaraju M;Bihler H;Mense M;Tearney GJ;Rowe SM;Engelhardt JF;Regev A;Rajagopal J
通讯作者：
Rajagopal J