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Advances in TNF Family Research pp 35–44Cite as

High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 691))

Abstract

Lymphotoxin (LT) is crucial for the regulation of HEV adhesion molecules MAdCAM-1 and PNAd and a sulfotransferase, GlcNAc6ST-2 (gene symbol Chst4); here called HEC-6ST. Following immunization, some HEVs express markers of both HEVs (PNAd) and LVs (LYVE-1). In order to evaluate this process in real time, we have developed mice transgenic for a construct that consists of an HEV specific gene driving a green fluorescent reporter gene (eGFP). These mice express the reporter gene in HEVs in concurrence with the endogenous gene and PNAd. Additional mice transgenic for lymphatic vessel reporter constructs are in development. These will provide material for in vivo imaging and allow us to evaluate the regulation and interaction of HEVs and LVs.

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Abbreviations

LN:

lymph node

PLN:

peripheral lymph node

LTβR:

lymphotoxin-β receptor

LV:

lymphatic vessel

HEV:

high endothelial venule

PNAd:

peripheral node addressin

HEC-6ST:

high endothelial cell sulfotransferase, HEC-GlcNA6ST, GlcNAc6ST-2, N-acetyl glucosamine 6-O-sulfotransferase-2; carbohydrate (chondroitin 6/keratan) sulfotransferase 4

MAdCAM-1:

mucosal addressin cell adhesion molecule 1

GlyCAM-1:

glycosylation-dependent cell adhesion molecule-1

OX:

oxazolone

LYVE-1:

lymphatic vessel endothelial hyaluronan receptor 1

GFP:

green fluorescent protein

L-sel:

L-selectin

PROX1:

prospero-related homeobox 1

References

  1. Ruddle NH, Akirav EM (2009) Secondary lymphoid organs: responding to genetic and environmental cues in ontogeny and the immune response. J Immunol 183:2205–2212

    Article  CAS  PubMed  Google Scholar 

  2. Mebius RE, Streeter PR, Michie S, Butcher EC, Weissman IL (1996) A developmental switch in lymphocyte homing receptor and endothelial vascular addressin expression regulates lymphocyte homing and permits CD4+CD3- cells to colonize lymph nodes. Proc Natl Acad Sci 93:11019–11024

    Article  CAS  PubMed  Google Scholar 

  3. Bistrup A, Bhakta S, Lee JK, Belov YY, Gunn MD, Zuo FR, Huang CC, Kannagi R, Rosen SD, Hemmerich S (1999) Sulfotransferases of two specificities function in the reconstitution of high endothelial cell ligands for L-selectin. J Cell Biol 145:899–910

    Article  CAS  PubMed  Google Scholar 

  4. Hiraoka N, Petryniak B, Nakayama J, Tsuboi S, Suzuki M, Yeh JC, Izawa D, Tanaka T, Miyasaka M, Lowe JB, Fukuda M (1999). A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis(x), an L-selectin ligand displayed by CD34. Immunity 11:79–89

    Article  CAS  PubMed  Google Scholar 

  5. Cuff CA, Sacca R, Ruddle NH (1999) Differential induction of adhesion molecule and chemokine expression by LTalpha3 and LTalphabeta in inflammation elucidates potential mechanisms of mesenteric and peripheral lymph node development. J Immunol 162:5965–5972

    CAS  PubMed  Google Scholar 

  6. Cuff CA, Schwartz J, Bergman CM, Russell KS, Bender JR, Ruddle NH (1998) Lymphotoxin alpha3 induces chemokines and adhesion molecules: insight into the role of LT alpha in inflammation and lymphoid organ development. J Immunol 161:6853–6860

    CAS  PubMed  Google Scholar 

  7. Drayton DL, Ying X, Lee J, Lesslauer W, Ruddle NH (2003) Ectopic LT alpha beta directs lymphoid organ neogenesis with concomitant expression of peripheral node addressin and a HEV-restricted sulfotransferase. J Exp Med 197:1153–1163

    Article  CAS  PubMed  Google Scholar 

  8. Kratz A, Campos-Neto A, Hanson MS, Ruddle NH (1996) Chronic inflammation caused by lymphotoxin is lymphoid neogenesis. J Exp Med 183:1461–1472

    Article  CAS  PubMed  Google Scholar 

  9. Sacca R, Cuff CA, Lesslauer W, Ruddle NH (1998) Differential activities of secreted lymphotoxin-alpha3 and membrane lymphotoxin-alpha1beta2 in lymphotoxin-induced inflammation: critical role of TNF receptor 1 signaling. J Immunol 160:485–491

    CAS  PubMed  Google Scholar 

  10. Drayton DL, Bonizzi G, Ying X, Liao S, Karin M, Ruddle NH (2004) I kappaB kinase complex alpha kinase activity controls chemokine and high endothelial venule gene expression in lymph nodes and nasal-associated lymphoid tissue. J Immunol 173:6161–6168

    CAS  PubMed  Google Scholar 

  11. Mounzer RM, Svendsen OS, Baluk P, Bergman CM, Padera TP, Wiig H, Jain RK, McDonald DM, Ruddle NH (2010). Lymphotoxin alpha contributes to lymphangiogenesis. Blood June 21 Epub ahead of print.

    Google Scholar 

  12. Liao S, Ruddle NH (2006) Synchrony of high endothelial venules and lymphatic vessels revealed by immunization. J Immunol 177:3369–3379

    CAS  PubMed  Google Scholar 

  13. DeTogni P, Goellner J, Ruddle NH, Streeter PR, Fick A, Mariathasan S, Smith SC, Carlson R, Shornick LP, Strauss-Schoenberger J et al (1994) Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 264:703–707

    Article  CAS  Google Scholar 

  14. Koni PA, Sacca R, Lawton P, Browning JL, Ruddle NH, Flavell RA (1997) Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 6:491–500

    Article  CAS  PubMed  Google Scholar 

  15. Liao S, Bentley K, Lebrun M, Lesslauer W, Ruddle FH, Ruddle NH (2007) Transgenic LacZ under control of Hec-6st regulatory sequences recapitulates endogenous gene expression on high endothelial venules. Proc Natl Acad Sci USA 104:4577–4582

    Article  CAS  PubMed  Google Scholar 

  16. Bradshaw MS, Bollekens JA, Ruddle FH (1995) A new vector for recombination-based cloning of large DNA fragments from yeast artificial chromosomes. Nucleic Acids Res 23:4850–4856

    Article  CAS  PubMed  Google Scholar 

  17. Shashikant CS, Carr JL, Bhargava J, Bentley KL, Ruddle FH (1998) Recombinogenic targeting: a new approach to genomic analysis–a review. Gene 223:9–20

    Article  CAS  PubMed  Google Scholar 

  18. Bistrup A, Tsay D, Shenoy P, Singer MS, Bangia N, Luther SA, Cyster JG, Ruddle NH, Rosen SD (2004) Detection of a sulfotransferase (HEC-GlcNAc6ST) in high endothelial venules of lymph nodes and in high endothelial venule-like vessels within ectopic lymphoid aggregates: relationship to the MECA-79 epitope. Am J Pathol 164:1635–1644

    CAS  PubMed  Google Scholar 

  19. Oliver G (2004) Lymphatic vasculature development. Nat Rev Immunol 4:35–45

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Myriam Hill for figure preparation and Myriam Hill and Daniel Reagan for outstanding technical assistance. This work was supported by U.S. Public Health Service Grants R01 DK057731 and CA016885 (to N.H.R.) and GM09966 (to F.H.R.) from the National Institutes of Health, a Mount Holyoke College Faculty Research Fellowship (to S.S) and a Lymphatic Research Foundation Fellowship (to R.A.M.)

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Authors and Affiliations

  1. Department of Epidemiology and Public Health, Yale University School of Medicine, 10 Amistad Street, P.O. Box 208089, New Haven, CT, 06520, USA

    Kevin L. Bentley, Shan Liao, Rawad M. Mounzer & Nancy H. Ruddle

  2. Department of Biological Sciences, Mount Holyoke College, South Hadley, MA, 01075, USA

    Sharon Stranford

  3. Department of Radiation Oncology, E.L. Steele Laboratory for Tumor Biology, Massachusetts General Hospital, 100 Blossom St., Cox 7, Boston, MA, 02114, USA

    Shan Liao

  4. Department of Internal Medicine, UPMC Montefiore Hospital, N-713, 200 Lothrop St., Pittsburgh, PA, 15213, USA

    Rawad M. Mounzer

  5. Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT, 06510, USA

    Frank H. Ruddle

  6. Departments of Epidemiology and Public Health and Immunobiology, Yale University School of Medicine, New Haven, CT, USA

    Nancy H. Ruddle

Authors
  1. Kevin L. Bentley
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  2. Sharon Stranford
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  3. Shan Liao
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  4. Rawad M. Mounzer
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  5. Frank H. Ruddle
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  6. Nancy H. Ruddle
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Corresponding author

Correspondence to Nancy H. Ruddle .

Editor information

Editors and Affiliations

  1. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    David Wallach

  2. Dept. Biological Chemistry, Weizmann Institute of Science, 1 Herzl Street, Rehovot, 76100, Israel

    Andrew Kovalenko

  3. Kennedy Institute of Rheumatology, Imperial College London, Aspenlea Rd. 1, London, W6 8LH, United Kingdom

    Marc Feldmann

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Bentley, K.L., Stranford, S., Liao, S., Mounzer, R.M., Ruddle, F.H., Ruddle, N.H. (2011). High Endothelial Venule Reporter Mice to Probe Regulation of Lymph Node Vasculature. In: Wallach, D., Kovalenko, A., Feldmann, M. (eds) Advances in TNF Family Research. Advances in Experimental Medicine and Biology, vol 691. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6612-4_4

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