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Lymph node lymphatic endothelial cells as multifaceted gatekeepers in the immune system

Akira Takeda1, Marko Salmi2, Sirpa Jalkanen2

  • 1MediCity and InFLAMES Flagship, University of Turku, Turku, Finland.

Trends in Immunology
|December 3, 2022
PubMed

Insights

Lymphatic endothelial cells (LECs) in lymph nodes have diverse immune roles, guiding cell traffic and managing antigens. Targeting these cells could modulate immune responses in disease.

Area of Science:

  • Immunology
  • Cell Biology
  • Vascular Biology

Background:

  • Single-cell technologies enable detailed characterization of lymphatic endothelial cell (LEC) subsets within lymph node (LN) sinus systems.
  • LECs reside in various LN locations, including subcapsular, paracortical, and medullary sinuses.
  • Emerging evidence highlights critical immunological functions of LECs within the LN stroma during immune responses.

Purpose of the Study:

  • To review and synthesize current knowledge on the immunological functions of distinct lymphatic endothelial cell (LEC) subsets in lymph nodes (LNs).
  • To discuss the roles of different LEC types in leukocyte and cancer cell trafficking, microbial capture, and antigen handling.
  • To highlight specific adaptations in human LECs and identify knowledge gaps relevant to human diseases.

Main Methods:

  • Review of recent literature utilizing single-cell technologies.
  • Analysis of studies investigating LEC functions in mouse and human lymph nodes.
  • Synthesis of data on cell trafficking, antigen presentation, and immune modulation by LECs.

Main Results:

  • Identification of multiple LEC subsets in various lymph node sinus compartments.
  • Demonstration of diverse LEC functions including leukocyte/cancer cell guidance, microbial capture, and antigen transport/presentation/storage.
  • Observation of specific adaptations in human LECs compared to murine models.

Conclusions:

  • Lymphatic endothelial cells (LECs) play multifaceted roles in immune responses within lymph nodes.
  • Understanding LEC functions is crucial for advancing clinical translation in inflammation and metastasis.
  • LN LECs represent promising targets for modulating immunoreactivity in disease settings.

Keywords:
antigen transportimmune responsesleukocyteslymph nodeslymphatic endothelial cellsmigrationsinuses

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