期刊
NATURE IMMUNOLOGY
卷 15, 期 10, 页码 982-U129出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.2983
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资金
- US National Institutes of Health [R37 GM37734, R37 AI047822, R01 AI093981, R01 DK084647, 5T32AI007290, 5T32CA009151, F32CA180415, R01 AI50143]
- US Department of Veterans Affairs
- Klaus Bensch Professorship
- Deutsche Forschungsgemeinschaft [KI1646/1-2]
- Stanford Institute for Immunity, Transplantation and Infection
- American Heart Association
- Crohn's and Colitis Foundation of America [3782]
- Grants-in-Aid for Scientific Research [24390018] Funding Source: KAKEN
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.
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