Langerhans Cells-Programmed by the Epidermis.
Langerhans Cells-Programmed by the Epidermis.
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DOI：
10.3389/fimmu.2017.01676
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发表时间：
2017
影响因子：
7.3
通讯作者：
Polak ME
中科院分区：
文献类型：
--
作者：
Clayton K;Vallejo AF;Davies J;Sirvent S;Polak ME
郎格汉斯细胞(LCS)以致密的免疫系统哨兵网络存在于表皮中。这些细胞通过解释它们遇到外来物质的微环境环境来确定适当的适应性免疫反应(炎症或耐受性)。在正常的生理“非危险”情况下，LCS协调免疫耐受的持续状态，防止不必要和有害的免疫激活。相反，当它们感觉到危险信号时，例如在感染期间或当皮肤的物理完整性因创伤而受损时，它们会指示适应性免疫系统的T淋巴细胞建立有效的效应器反应。最近对LC和表皮微环境之间串扰的分子机制的研究进展揭示了其对编程LC生物学的重要性。本文通过对转录程序和基因调控网络(GRN)的分析，总结了描述LC起源和功能的新发现。对公开可用的数据集的回顾和荟萃分析清楚地将LC描述为不同于传统的树突状细胞(DC)和巨噬细胞，这表明表皮微环境在编程LC生物学中起着主要作用。这一概念进一步得到了对表皮促炎信号的影响的分析支持，该信号调节人类和小鼠LC中的关键GRN。应用全转录组分析和电子计算机分析，促进了我们对LCS如何接收、整合和处理来自稳态和病变表皮的信号的理解。有趣的是，在动态平衡和免疫应激下，LCS中的分子网络保持相对稳定，反映了与组织定位相关的关键进化需要。重要的是，为了发挥其在协调抗病毒适应性免疫反应中的关键作用，LC与其他类型的DC共享特定的转录模块，能够将抗原交叉递送到细胞毒CD8+T细胞，这表明可能存在进化收敛机制。随着更先进的技术的发展，可以在染色质组织、组蛋白修饰、蛋白质翻译和磷酸化水平上描绘分子网络，未来的组学研究将带来对支撑人类LC生物学的复杂分子机制的深入了解。
Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, “non-dangerous” situation, LCs coordinate a continuous state of immune tolerance, preventing unnecessary and harmful immune activation. Conversely, when they sense a danger signal, for example during infection or when the physical integrity of skin has been compromised as a result of a trauma, they instruct T lymphocytes of the adaptive immune system to mount efficient effector responses. Recent advances investigating the molecular mechanisms underpinning the cross talk between LCs and the epidermal microenvironment reveal its importance for programming LC biology. This review summarizes the novel findings describing LC origin and function through the analysis of the transcriptomic programs and gene regulatory networks (GRNs). Review and meta-analysis of publicly available datasets clearly delineates LCs as distinct from both conventional dendritic cells (DCs) and macrophages, suggesting a primary role for the epidermal microenvironment in programming LC biology. This concept is further supported by the analysis of the effect of epidermal pro-inflammatory signals, regulating key GRNs in human and murine LCs. Applying whole transcriptome analyses and in silico analysis has advanced our understanding of how LCs receive, integrate, and process signals from the steady-state and diseased epidermis. Interestingly, in homeostasis and under immunological stress, the molecular network in LCs remains relatively stable, reflecting a key evolutionary need related to tissue localization. Importantly, to fulfill their key role in orchestrating antiviral adaptive immune responses, LC share specific transcriptomic modules with other DC types able to cross-present antigens to cytotoxic CD8+ T cells, pointing to a possible evolutionary convergence mechanism. With the development of more advanced technologies allowing delineation of the molecular networks at the level of chromatin organization, histone modifications, protein translation, and phosphorylation, future “omics” investigations will bring in-depth understanding of the complex molecular mechanisms underpinning human LC biology.
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影响因子：
2.2
作者：
Carpentier S;Vu Manh TP;Chelbi R;Henri S;Malissen B;Haniffa M;Ginhoux F;Dalod M
通讯作者：
Dalod M
影响因子：
7.3
作者：
Cheng CS;Feldman KE;Lee J;Verma S;Huang DB;Huynh K;Chang M;Ponomarenko JV;Sun SC;Benedict CA;Ghosh G;Hoffmann A
通讯作者：
Hoffmann A
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。
DOI：
10.1084/jem.20091586
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chorro L;Sarde A;Li M;Woollard KJ;Chambon P;Malissen B;Kissenpfennig A;Barbaroux JB;Groves R;Geissmann F
通讯作者：
Geissmann F
DOI：
10.4049/jimmunol.1102613
发表时间：
2012-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bajaña S;Roach K;Turner S;Paul J;Kovats S
通讯作者：
Kovats S
影响因子：
4
作者：
Behar, Marcelo;Hoffmann, Alexander
通讯作者：
Hoffmann, Alexander