Proteomics of matrix production - FRCs

Data to accompany figure S2Proteomics of FRC-derived matricesIn vitro FRC cell line-derived matrices generated after 5 days in culture were subjected to proteomic analysis by mass spectrometry. Summary data in xls spreadsheet. SWATH dataset uploaded to PRIDE repository ID=PXD015816http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD015816AbstractLymph nodes (LNs) work as filtering organs, constantly sampling peripheral cues. This is facilitated by the conduit network, a parenchymal tubular-like structure formed of bundles of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 5-fold expansion with every adaptive immune response and yet these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering functions are affected during cycles of LN expansion and resolution is not known. Here we show that the conduit structure is disrupted during acute LN expansion but FRC-FRC contacts remain intact. In homeostasis, polarised FRCs adhere to the underlying substrate to deposit ECM ba-solaterally. ECM production by FRCs is regulated by the C-type lectin CLEC-2, expressed by dendritic cells (DCs), at transcriptional and secretory levels. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, which allows soluble antigens to reach more antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism that enables LNs to prevent inflammation-induced fibrosis.HighlightsFRCs use polarized microtubule networks to guide matrix depositionCLEC-2/PDPN controls matrix production at transcriptional and post-transcriptional levelsFRCs halt matrix production and decouple from conduits during acute LN expansionConduits leak soluble antigen during acute LN expansion

伴随图S2的FRC来源的蛋白质组学数据
体外培养5天后由FRC细胞系衍生的基质样本，经过质谱分析进行蛋白质组学检测。总结数据以xls表格形式呈现。SWATH数据集已上传至PRIDE数据库，ID=PXD015816
http://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD015816摘要
淋巴结（LNs）作为过滤器官，持续采样周围信号。这一过程得益于导管网络，即由纤维母细胞网状细胞（FRCs）包裹的排列整齐的细胞外基质（ECM）纤维束形成的类似管状的实质结构。淋巴结在每次适应性免疫反应中都会扩大5倍，然而这些富含ECM的结构并未遭受永久性损伤。导管完整性和过滤功能在淋巴结的扩大和缓解周期中是否受到影响尚不清楚。本研究表明，在急性淋巴结扩大期间，导管结构受到破坏，但FRC-FRC接触保持完整。在稳态下，极化的FRCs附着于下层的基质上，沉积ECM。FRCs产生的ECM受树突状细胞（DCs）表达的C型凝集素CLEC-2在转录和分泌水平上的调控。炎症性淋巴结维持导管的分子量排除性，但流动性变得泄漏，允许可溶性抗原到达更多的抗原呈递细胞。本研究展示了在免疫反应过程中，外周组织和淋巴结之间的动态通信如何变化，并描述了一种机制，使淋巴结能够防止炎症引起的纤维化。
亮点
FRCs利用极化的微管网络引导基质沉积
CLEC-2/PDPN在转录和转录后水平上控制基质产生
在急性淋巴结扩大期间，FRCs停止基质产生并从导管中分离
在急性淋巴结扩大期间，导管泄漏可溶性抗原