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

Nat. Immunol.2015 Jan;16(1):75-84. Epub 2014 Oct 27
Jillian L Astarita 1 , Viviana Cremasco 2 , Jianxin Fu 3 , Max C Darnell 4 , James R Peck 2 , Janice M Nieves-Bonilla 2 , Kai Song 3 , Yuji Kondo 3 , Matthew C Woodruff 5 , Alvin Gogineni 6 , Lucas Onder 7 , Burkhard Ludewig 7 , Robby M Weimer 6 , Michael C Carroll 8 , David J Mooney 4 , Lijun Xia 3 , Shannon J Turley 9
Jillian L Astarita 1 , Viviana Cremasco 2 , Jianxin Fu 3 , Max C Darnell 4 , James R Peck 2 , Janice M Nieves-Bonilla 2 , Kai Song 3 , Yuji Kondo 3 , Matthew C Woodruff 5 , Alvin Gogineni 6 , Lucas Onder 7 , Burkhard Ludewig 7 , Robby M Weimer 6 , Michael C Carroll 8 , David J Mooney 4 , Lijun Xia 3 , Shannon J Turley 9
+ et al

[No authors listed]

Author information
  • 1 1] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • 2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
  • 3 1] Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA. [2] Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
  • 4 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts, USA. [2] Wyss Institute for Biologically Inspired Engineering at Harvard University, Cambridge, Massachusetts, USA.
  • 5 1] Division of Medical Sciences, Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
  • 6 Department of Biomedical Imaging, Genentech, South San Francisco, California, USA.
  • 7 Institute of Immunobiology, Kantonal Hospital St. Gallen, St. Gallen, Switzerland.
  • 8 Program in Cellular and Molecular Medicine, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
  • 9 1] Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Cancer Immunology, Genentech, South San Francisco, California, USA.
全文

摘要


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.