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Cited by 411T-cell and B-cell ImmunologyChemokine receptors and signalingDiabetes and associated disorders

Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response

Open access
Zhang, Nan, Schröppel, Bernd, Lal, Girdhari, Jakubzick, Claudia, Mao, Xia, Chen, Dan, Yin, Na, Jessberger, Rolf +3 more·2009·Immunity
DOI 10.1016/j.immuni.2008.12.022PMC PMC2737741
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Abstract

To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chemokine receptors CCR2, CCR4, and CCR5 and P- and E-selectin ligands. In the allograft, Treg cells were activated and subsequently migrated to the draining lymph nodes (dLNs) in a CCR2, CCR5, and CCR7 fashion; this movement was essential for optimal suppression. Treg cells inhibited dendritic cell migration in a TGF-beta and IL-10 dependent fashion and suppressed antigen-specific T effector cell migration, accumulation, and proliferation in dLNs and allografts. These results showed that sequential migration from blood to the target tissue and to dLNs is required for Treg cells to differentiate and execute fully their suppressive function.

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  • Tregs employ a cell-surface-bound form of the cytokine lymphotoxin for transmigration into initial LVs.

    “Tregs employ a cell-surface-bound form of the cytokine lymphotoxin for transmigration (118).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [118]

    The Discussion (page unavailable) reports that Tregs migrate from grafts through afferent lymphatics to draining lymph nodes and that CCR7 is required for this route. It does not say they use cell-surface-bound lymphotoxin for transmigration; searches for lymphotoxin and membrane-bound LTαβ found no supporting passage. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Binding of Treg lymphotoxin to the lymphotoxin receptor on capillary LECs promotes lamellipodia formation on LECs that contain VCAM and promote transmigration.

    “Binding of Treg lymphotoxin to the lymphotoxin receptor expressed on capillary LECs promotes lamellipodia formation on LECs that contain VCAM and promote transmigration (118, 119).”

    From Transport and Immune Functions of the Lymphatic System. (2025) · cites this paper as [118]

    The Discussion reports that Treg exit grafts through afferent lymphatics and that CCR7 regulates this migration. It does not describe Treg lymphotoxin binding to receptors on capillary lymphatic endothelial cells, VCAM-containing lamellipodia, or that mechanism of transmigration; searches for those terms found no supporting passage. No page number was provided in our copy. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cites

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Cited by

Sorted by citations

Authors
Zhang, N., Schröppel, B., Lal, G., Jakubzick, C., Mao, X., Chen, D., Yin, N., Jessberger, R., Ochando, J. C., Ding, Y., & Bromberg, J. S.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Technische Universität Dresden (DE)
  • Instituto de Salud Carlos III (ES)
Corresponding author
Bromberg, Jonathan S.
ORCID
Venue
Immunity
Publisher
Elsevier BV
Published
2009-03
Volume
30
Issue
3
Pages
458-469
ISSN
1074-7613 (ISSN-L)
DOI
10.1016/j.immuni.2008.12.022
PMC
PMC2737741
OpenAlex
W2055603849
Cited by
411
References
0
Citations by year
2026: 12 · 2025: 10 · 2024: 20 · 2023: 15 · 2022: 20 · 2021: 35 · 2020: 25 · 2019: 23 · 2018: 17 · 2017: 35 · 2016: 22 · 2015: 22 · 2014: 22 · 2013: 30 · 2012: 26
FWCI
14.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Funders
National Institute of Allergy and Infectious Diseases (R01 AI-62765, R01AI041428, R01 AI-44929, K08AI071038, R01AI044929, R01AI062765, R37AI062765)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
regulatory T cells, Treg cell migration, islet allografts, draining lymph nodes, chemokine receptors, CCR2, CCR5, CCR7, CCR4, selectins, dendritic cell migration, TGF-beta, IL-10, Treg differentiation
MeSH terms
Animals, Cell Movement, Cells, Cultured, Dendritic Cells, Inflammation, Islets of Langerhans, Lymph Nodes, Mice, Inbred BALB C, Mice, Inbred C57BL, Autoimmunity, Lymphocyte Subsets, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Mice

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