Abstract
In lymph nodes, fibroblastic reticular cells (FRCs) form a collagen-based reticular network that supports migratory dendritic cells (DCs) and T cells and transports lymph. A hallmark of FRCs is their propensity to contract collagen, yet this function is poorly understood. Here we demonstrate that podoplanin (PDPN) regulates actomyosin contractility in FRCs. Under resting conditions, when FRCs are unlikely to encounter mature DCs expressing the PDPN receptor CLEC-2, PDPN endowed FRCs with contractile function and exerted tension within the reticulum. Upon inflammation, CLEC-2 on mature DCs potently attenuated PDPN-mediated contractility, which resulted in FRC relaxation and reduced tissue stiffness. Disrupting PDPN function altered the homeostasis and spacing of FRCs and T cells, which resulted in an expanded reticular network and enhanced immunity.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amides / pharmacology
-
Animals
-
Cell Survival / immunology
-
Collagen / immunology
-
Collagen / metabolism*
-
Cytoskeleton / immunology
-
Cytoskeleton / ultrastructure
-
Enzyme Inhibitors / pharmacology
-
Female
-
Fibroblasts / cytology*
-
Fibroblasts / immunology
-
Fibroblasts / ultrastructure
-
Lectins, C-Type / immunology
-
Lectins, C-Type / metabolism*
-
Lymph Nodes / cytology*
-
Lymph Nodes / immunology
-
Lymph Nodes / ultrastructure
-
Male
-
Membrane Glycoproteins / immunology
-
Membrane Glycoproteins / metabolism*
-
Mice, 129 Strain
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Microscopy, Confocal
-
Phosphorylation
-
Pyridines / pharmacology
-
Specific Pathogen-Free Organisms
Substances
-
Amides
-
CLEC-2 protein, mouse
-
Enzyme Inhibitors
-
Gp38 protein, mouse
-
Lectins, C-Type
-
Membrane Glycoproteins
-
Pyridines
-
Y 27632
-
Collagen