title: Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing.
abstract: 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.
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Mike
authors.initials: M
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Helena
authors.initials: H
authors.lastname: Kiefel
authors.affiliation: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: LaJevic
authors.affiliation: Departments of Cell and Molecular Biology, Immunology and Microbial Science, and Chemical Physiology, The Scripps Research Institute, La Jolla, California USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Macauley
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
authors.affiliation: Palo Alto Veterans Institute for Research, Palo Alto, California, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: O'Hara
authors.affiliation: Palo Alto Veterans Institute for Research, Palo Alto, California, USA.
authors.forename: Junliang
authors.initials: J
authors.lastname: Pan
authors.affiliation: Departments of Cell and Molecular Biology, Immunology and Microbial Science, and Chemical Physiology, The Scripps Research Institute, La Jolla, California USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.affiliation: 1] Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA. [2] Palo Alto Veterans Institute for Research, Palo Alto, California, USA. [3] The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.
authors.forename: Eugene C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism*; D002465:Cell Movement / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D063990:Gene Ontology; D008198:Lymph Nodes / Q000098:blood supply; D008214:Lymphocytes / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000098:blood supply*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D014699:Venules / Q000378:metabolism*