Publication

The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture

Journal Paper/Review - Oct 27, 2014

Units
PubMed
Doi

Citation
Astarita J, Xia L, Mooney D, Carroll M, Weimer R, Ludewig B, Onder L, Gogineni A, Woodruff M, Kondo Y, Song K, Nieves-Bonilla J, Peck J, Darnell M, Fu J, Cremasco V, Turley S. The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture. Nat Immunol 2014; 16:75-84.
Type
Journal Paper/Review (English)
Journal
Nat Immunol 2014; 16
Publication Date
Oct 27, 2014
Issn Electronic
1529-2916
Pages
75-84
Brief description/objective

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.