Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS, UPS, Toulouse, France.
Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), UMR1048, INSERM, UPS, Toulouse, France; Plateforme Genome et Transcriptome (GeT), Genopole Toulouse, Toulouse, France.
Cell Rep. 2019 Mar 12;26(11):3116-3131.e5. doi: 10.1016/j.celrep.2019.02.042.
High-endothelial venules (HEVs) are specialized blood vessels allowing recirculation of naive lymphocytes through lymphoid organs. Here, using full-length, single-cell RNA sequencing, RNA fluorescence in situ hybridization (FISH), flow cytometry, and immunohistofluorescence, we reveal the heterogeneity of HEVs in adult mouse peripheral lymph nodes (PLNs) under conditions of homeostasis, antigenic stimulation, and after inhibition of lymphotoxin-β receptor (LTβR) signaling. We demonstrate that HEV endothelial cells are in an activated state during homeostasis, and we identify the genes characteristic of the differentiated HEV phenotype. We show that LTβR signaling regulates many HEV genes and pathways in resting PLNs and that immune stimulation induces a global and temporary inflammatory phenotype in HEVs without compromising their ability to recruit naive lymphocytes. Most importantly, we uncover differences in the regulation of genes controlling lymphocyte trafficking, Glycam1, Fut7, Gcnt1, Chst4, B3gnt3, and Ccl21a, that have implications for HEV function and regulation in health and disease.
高内皮微静脉 (HEV) 是一种特殊的血管，允许幼稚淋巴细胞在淋巴器官中再循环。在这里，我们使用全长单细胞 RNA 测序、RNA 荧光原位杂交 (FISH)、流式细胞术和免疫荧光，揭示了在稳态、抗原刺激和抑制淋巴毒素-β 受体 (LTβR) 信号后，成年小鼠外周淋巴结 (PLN) 中 HEV 的异质性。我们证明了 HEV 内皮细胞在稳态下处于激活状态，并鉴定了分化的 HEV 表型特征的基因。我们表明，LTβR 信号在静止的 PLN 中调节许多 HEV 基因和途径，而免疫刺激诱导 HEV 中出现全身性和暂时性炎症表型，而不会损害它们招募幼稚淋巴细胞的能力。最重要的是，我们揭示了控制淋巴细胞迁移的基因的调控差异，包括 Glycam1、Fut7、Gcnt1、Chst4、B3gnt3 和 Ccl21a，这些差异对 HEV 在健康和疾病中的功能和调控具有重要意义。
