Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing

• Published in: Nature immunology Vol. 15; no. 10; pp. 982 - 995
• Main Authors: Lee, Mike, Kiefel, Helena, LaJevic, Melissa D, Macauley, Matthew S, Kawashima, Hiroto, O'Hara, Edward, Pan, Junliang, Paulson, James C, Butcher, Eugene C
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2014; Nature Publishing Group
• Subjects: 13/31; 14/19; 38; 38/39; 38/61; 631/1647/2017/2079; 631/250; 631/250/1619/40; 631/250/1620; 64/60; 82/1; 82/51; 96/34; Animals; Biomedicine; Blood; Capillaries - metabolism; Cell Movement - genetics; Endothelial Cells - metabolism; Endothelium - cytology; Endothelium - metabolism; Female; Flow Cytometry; Gene Expression Profiling; Gene Ontology; Immune response; Immunology; Infectious Diseases; Lymph Nodes - blood supply; Lymphocytes; Lymphocytes - metabolism; Lymphoid Tissue - blood supply; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Oligonucleotide Array Sequence Analysis; Properties; Regulation; resource; Tissues; Venules - metabolism
• ISSN: 1529-2908; 1529-2916; 1529-2916
• DOI: 10.1038/ni.2983

High endothelial vessels (HEVs) provide the conduit for blood-borne leukocytes to enter lymph nodes. Butcher and colleagues report transcriptional profiles of various endothelial cell populations that can explain functional differences of homing-molecule modifications. Lymphocytes are recruited from blood by high-endothelial venules (HEVs). We performed transcriptomic analyses and identified molecular signatures that distinguish HEVs from capillary endothelium and that define tissue-specific HEV specialization. Capillaries expressed gene programs for vascular development. HEV-expressed genes showed enrichment for genes encoding molecules involved in immunological defense and lymphocyte migration. We identify capillary and HEV markers and candidate mechanisms for regulated recruitment of lymphocytes, including a lymph node HEV–selective transmembrane mucin; transcriptional control of functionally specialized carbohydrate ligands for lymphocyte L-selectin; HEV expression of molecules for transendothelial migration; and metabolic programs for lipid mediators of lymphocyte motility and chemotaxis. We also elucidate a carbohydrate-recognition pathway that targets B cells to intestinal lymphoid tissues, defining CD22 as a lectin-homing receptor for mucosal HEVs.