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

2014; Nature Portfolio; Volume: 16; Issue: 1 Linguagem: Inglês

10.1038/ni.3035

1529-2916

Jillian L. Astarita, Viviana Cremasco, Jianxin Fu, Max Darnell, James R. Peck, Janice M Nieves-Bonilla, Kai Song, Yuji Kondo, Matthew C. Woodruff, Alvin Gogineni, Lucas Onder, Burkhard Ludewig, Robby M. Weimer, Michael C. Carroll, David Mooney, Lijun Xia, Shannon J. Turley,

Lymphatic System and Diseases

Lymph nodes expand after an inflammatory challenge to accommodate their increased cellularity. Turley and colleagues show that fibroblastic reticular cells regulate this expansion process through the interaction of podoplanin with its receptor CLEC-2 expressed on incoming dendritic cells. 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.