Dendritic cells control fibroblastic reticular network tension and lymph node expansion

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Lymph node expansion is a hallmark of adaptive immunity, driven by lymphocyte proliferation and influx.
• The physical properties and elasticity of lymph nodes are crucial for accommodating this expansion.
• Stromal fibroblastic reticular cells (FRCs) form the lymph node network, influencing its mechanical properties.

Purpose of the Study:

• To investigate the role of podoplanin (PDPN) and CLEC-2 signaling in regulating lymph node elasticity and expansion.
• To elucidate the molecular mechanisms by which dendritic cells modulate FRC behavior during immune responses.

Main Methods:

• In vitro studies using mouse cells to analyze PDPN-mediated signaling pathways.
• In vivo experiments using genetically modified mice lacking CLEC-2 in dendritic cells.
• Administration of CLEC-2 protein to immunized wild-type mice.

Main Results:

• Podoplanin (PDPN) signaling in FRCs induces actomyosin contractility via RhoA/C and ROCK.
• Dendritic cell-expressed CLEC-2 binds to PDPN, causing clustering and uncoupling from RhoA/C, leading to FRC relaxation.
• CLEC-2 administration enhanced lymph node expansion in immunized mice.
• Loss of CLEC-2 in dendritic cells significantly constrained lymph node expansion.

Conclusions:

• Dendritic cells actively remodel lymph nodes by modulating PDPN signaling in FRCs through CLEC-2.
• This CLEC-2/PDPN interaction allows FRC network stretching, facilitating rapid lymph node expansion essential for adaptive immunity.