Modeling Structural Elements and Functional Responses to Lymphatic-Delivered Cues in a Murine Lymph Node on a Chip

Area of Science:

• Immunology
• In vitro modeling
• Cancer research

Background:

• Lymph nodes (LNs) are crucial for immune responses but lack accurate in vitro models.
• Understanding LN homeostasis and disease pathogenesis requires better experimental systems.

Purpose of the Study:

• To develop an engineered lymph node (eLN) model that recapitulates key in vitro functions of murine LNs.
• To investigate immune responses and stromal cell behavior within this eLN model.
• To explore the influence of cancer-derived factors on LN function.

Main Methods:

• Incorporation of primary murine lymphocytes, fibroblastic reticular cells, and lymphatic endothelial cells into an engineered construct.
• Mimicking LN cortex and paracortex architectures within the eLN.
• Challenging the eLN with stimuli to assess inflammatory and antigen-specific immune activation.

Main Results:

• The eLN model successfully replicated key cellular components and architectures of native LNs.
• The eLN demonstrated robust inflammatory and antigen-specific immune responses upon challenge.
• The model allowed real-time monitoring of immune activation and differentiation between non-specific and specific stimuli.
• The study investigated the impact of murine melanoma factors on eLN behavior.

Conclusions:

• The engineered lymph node (eLN) model provides a powerful platform for in vitro studies of LN biology.
• This model enhances understanding of both stromal and immune responses within LNs.
• The eLN facilitates the development of novel therapeutic strategies for improving LN function in disease settings, including cancer.