<p>Dendritic cells (DCs) play a pivotal role in adaptive immunity by migrating through lymphatic vessels (LVs) to lymph nodes (LNs), where they present antigens and initiate the immune response. The optimal DC migration is critical for the success of immunotherapies such as DC-based vaccines. However, current in vitro models often fail to replicate the complex architecture and function of human initial LVs, limiting detailed mechanistic studies of DC chemotaxis under controlled conditions. Here, we developed a three-dimensional (3D) microfluidic platform that recapitulates the blunt-ended structure of initial LVs, providing a physiologically relevant environment to investigate the chemotactic migration of DCs via CCR7–CCL21 axis. We examined (i) the influence of the LV microenvironment on DC movement, (ii) the impact of DC maturation on migratory behavior, and (iii) the impact of pre-inflamed LV on DC chemotaxis. Live-cell imaging followed by quantitative trajectory analysis demonstrated that LVs enhanced the directionality of DC migration, while mature DCs exhibited enhanced mobility. Under inflammatory conditions, characterized by elevated CCL21 level, further amplified both mobility and directionality, emphasizing the dynamic regulation of DC trafficking. This microfluidic 3D LV model offers a robust platform for investigating immune cell trafficking mechanisms, with potential applications in the development and optimization of cell-based immunotherapies.</p>

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A 3D Microfluidic Model of Initial Lymphatic Vessels for Investigating Dendritic Cell Chemotaxis Under Inflammatory Condition

  • Hyeonsu Jo,
  • Somin Lee,
  • Inae Park,
  • Mikang Shim,
  • James Yu,
  • Young Sun Oh,
  • Junsang Doh,
  • Young-Kwon Hong,
  • Noo Li Jeon

摘要

Dendritic cells (DCs) play a pivotal role in adaptive immunity by migrating through lymphatic vessels (LVs) to lymph nodes (LNs), where they present antigens and initiate the immune response. The optimal DC migration is critical for the success of immunotherapies such as DC-based vaccines. However, current in vitro models often fail to replicate the complex architecture and function of human initial LVs, limiting detailed mechanistic studies of DC chemotaxis under controlled conditions. Here, we developed a three-dimensional (3D) microfluidic platform that recapitulates the blunt-ended structure of initial LVs, providing a physiologically relevant environment to investigate the chemotactic migration of DCs via CCR7–CCL21 axis. We examined (i) the influence of the LV microenvironment on DC movement, (ii) the impact of DC maturation on migratory behavior, and (iii) the impact of pre-inflamed LV on DC chemotaxis. Live-cell imaging followed by quantitative trajectory analysis demonstrated that LVs enhanced the directionality of DC migration, while mature DCs exhibited enhanced mobility. Under inflammatory conditions, characterized by elevated CCL21 level, further amplified both mobility and directionality, emphasizing the dynamic regulation of DC trafficking. This microfluidic 3D LV model offers a robust platform for investigating immune cell trafficking mechanisms, with potential applications in the development and optimization of cell-based immunotherapies.