Fibroblastic Reticular Cells Control Conduit Matrix Deposition during Lymph Node Expansion

Area of Science:

• Immunology
• Cell Biology
• Tissue Engineering

Background:

• Lymph nodes (LNs) filter peripheral cues via a conduit network of extracellular matrix (ECM) and fibroblastic reticular cells (FRCs).
• LNs rapidly expand during immune responses, but the impact on conduit integrity and function remains unclear.

Purpose of the Study:

• To investigate the effects of acute lymph node expansion on the conduit network's structure and function.
• To elucidate the mechanisms regulating ECM deposition and its role in maintaining conduit integrity during inflammation.

Main Methods:

• Immunofluorescence microscopy to visualize conduit structures and FRC-FRC contacts.
• Analysis of ECM deposition and molecular regulators of ECM production.
• Assessment of conduit flow and size exclusion properties in inflamed LNs.

Main Results:

• Conduit structures are partially disrupted during acute LN expansion, yet FRC-FRC contacts remain intact.
• Polarized FRCs deposit ECM via LL5-β, with CLEC-2 on dendritic cells regulating ECM production.
• Inflamed LNs preserve size exclusion, and despite disrupted flow, conduit function persists.

Conclusions:

• Lymph node conduits exhibit remarkable robustness during rapid expansion, with partial disruption and persistent function.
• Dynamic communication between peripheral tissues and LNs, involving dendritic cell-CLEC-2 signaling, prevents inflammation-induced lymphoid tissue fibrosis.