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

Nature Immunology volume 15, pages 982995 (2014) | Download Citation

  • A Corrigendum to this article was published on 16 January 2015

This article has been updated


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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Change history

  • 27 October 2014

    In the version of this article initially published, Hiroto Kawashima was omitted as an author. The correct author list is as follows: Mike Lee1, Helena Kiefel1, Melissa D LaJevic1, Matthew S Macauley2, Hiroto Kawashima3, Edward O'Hara4, Junliang Pan4, James C Paulson2 & Eugene C Butcher1,4,5. The affiliation for this author is as follows: Department of Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan. The Author Contributions section should include "H.K. provided advice and the S2 hybridoma" (and the corresponding first thanks in Acknowledgments should be removed). The error has been corrected in the HTML and PDF versions of the article.


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We thank J. Sweere, A. Scholz, C. Czupalla and B. Arlian for help with experiments; J. Jang for antibody production; L. Rott for assistance with cell sorting; all members of the Butcher laboratory for discussions; B. Yoo (Stanford University) and T.A. Rando (Stanford University) for tissues from Hes1-EmGFPSAT mice; M. Salmi and M. Miyasaka for critical review of the manuscript; and the UniProt Consortium, the Kyoto Encyclopedia of Genes and Genomes, Enrichr software (E.Y. Chen, C.M. Tan, Y. Kou, Q. Duan, Z. Wang, G.V. Meirelles, N.R. Clark and Ma'ayan A. of the Icahn School of Medicine at Mount Sinai), iHOP (Information Hyperlinked over Proteins) online gene-guided access to PubMed abstracts, and the Immunological Genome Project for their informatics tools and compendia of data. Supported by the US National Institutes of Health (R37 GM37734, R37 AI047822, R01 AI093981 and R01 DK084647 to E.C.B.; 5T32AI007290 to M.L.; 5T32CA009151, 5T32AI007290 and F32CA180415 to M.D.L.; and R01 AI50143 to J.C.P.), the US Department of Veterans Affairs (E.C.B.), the Klaus Bensch Professorship (E.C.B.), Deutsche Forschungsgemeinschaft (KI1646/1-2 to H.Ki.), the Stanford Institute for Immunity, Transplantation and Infection (H.Ki.), the American Heart Association (H.Ki.) and the Crohn's and Colitis Foundation of America (Ref. 3782 to M.L.).

Author information


  1. Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

    • Mike Lee
    • , Helena Kiefel
    • , Melissa D LaJevic
    •  & Eugene C Butcher
  2. Departments of Cell and Molecular Biology, Immunology and Microbial Science, and Chemical Physiology, The Scripps Research Institute, La Jolla, California USA.

    • Matthew S Macauley
    •  & James C Paulson
  3. Department of Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.

    • Hiroto Kawashima
  4. Palo Alto Veterans Institute for Research, Palo Alto, California, USA.

    • Edward O'Hara
    • , Junliang Pan
    •  & Eugene C Butcher
  5. The Center for Molecular Biology and Medicine, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA.

    • Eugene C Butcher


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M.L. developed HEC-isolation protocols and designed and performed experiments, including flow cytometry of ECs, whole-genome expression analyses, immunohistology and homing studies; H.Ki. performed flow cytometry and immunofluorescence staining; M.D.L. performed immunoprecipitation and immunoblot analysis studies; M.S.M. did homing studies; H.Ka. provided advice and the S2 hybridoma; M.S.M. and J.C.P. contributed to writing of the section on HEV glycans; E.O. established the parameters for the isolation of RNA from HECs; J.P. provided intellectual input; and E.C.B. designed and guided the study, analyzed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eugene C Butcher.

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