Gregory Julia L, Walter Anne, Alexandre Yannick O, Hor Jyh Liang, Liu Ruijie, Ma Joel Z, Devi Sapna, Tokuda Nobuko, Owada Yuji, Mackay Laura K, Smyth Gordon K, Heath William R, Mueller Scott N
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
Department of Microbiology and Immunology, The University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia; The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, VIC 3000, Australia.
Cell Rep. 2017 Jan 10;18(2):406-418. doi: 10.1016/j.celrep.2016.12.038.
Lymph nodes (LNs) are constructed of intricate networks of endothelial and mesenchymal stromal cells. How these lymphoid stromal cells (LSCs) regulate lymphoid tissue remodeling and contribute to immune responses remains poorly understood. We performed a comprehensive functional and transcriptional analysis of LSC responses to skin viral infection and found that LSC subsets responded robustly, with different kinetics for distinct pathogens. Recruitment of cells to inflamed LNs induced LSC expansion, while B cells sustained stromal responses in an antigen-independent manner. Infection induced rapid transcriptional responses in LSCs. This transcriptional program was transient, returning to homeostasis within 1 month of infection, yet expanded fibroblastic reticular cell networks persisted for more than 3 months after infection, and this altered LN composition reduced the magnitude of LSC responses to subsequent heterologous infection. Our results reveal the complexity of LSC responses during infection and suggest that amplified networks of LN stromal cells support successive immune responses.
淋巴结（LNs）由内皮细胞和间充质基质细胞构成的复杂网络组成。这些淋巴样基质细胞（LSCs）如何调节淋巴组织重塑并促进免疫反应仍知之甚少。我们对LSCs对皮肤病毒感染的反应进行了全面的功能和转录分析，发现LSC亚群反应强烈，对不同病原体有不同的动力学。细胞募集到炎症性淋巴结会诱导LSC扩增，而B细胞以抗原非依赖方式维持基质反应。感染诱导LSCs快速的转录反应。这种转录程序是短暂的，在感染后1个月内恢复稳态，但感染后3个月以上，扩增的成纤维网状细胞网络仍然存在，并且这种改变的淋巴结组成降低了LSCs对后续异源感染反应的强度。我们的结果揭示了感染期间LSC反应的复杂性，并表明淋巴结基质细胞的扩增网络支持连续的免疫反应。
