Publication
The CLEC-2-podoplanin axis controls the contractility of fibroblastic reticular cells and lymph node microarchitecture
Journal Paper/Review - Oct 27, 2014
Astarita Jillian L, Xia Lijun, Mooney David J, Carroll Michael C, Weimer Robby M, Ludewig Burkhard, Onder Lucas, Gogineni Alvin, Woodruff Matthew C, Kondo Yuji, Song Kai, Nieves-Bonilla Janice M, Peck James R, Darnell Max C, Fu Jianxin, Cremasco Viviana, Turley Shannon J
Units
PubMed
Doi
Citation
Type
Journal
Publication Date
Issn Electronic
Pages
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.