Back to Search
Start Over
Dendritic cells control fibroblastic reticular network tension and lymph node expansion
- Source :
- Nature. October 23, 2014, Vol. 514 Issue 7523, p498, 15 p.
- Publication Year :
- 2014
-
Abstract
- After immunogenic challenge, infiltrating and dividing lymphocytes markedly increase lymph node cellularity, leading to organ expansion (1,2). Here we report that the physical elasticity of lymph nodes is maintained in part by podoplanin (PDPN) signalling in stromal fibroblastic reticular cells (FRCs) and its modulation by CLEC-2 expressed on dendritic cells. We show in mouse cells that PDPN induces actomyosin contractility in FRCs via activation of RhoA/C and downstream Rho-associated protein kinase (ROCK). Engagement by CLEC-2 causes PDPN clustering and rapidly uncouples PDPN from RhoA/C activation, relaxing the actomyosin cytoskeleton and permitting FRC stretching. Notably, administration of CLEC-2 protein to immunized mice augments lymph node expansion. In contrast, lymph node expansion is significantly constrained in mice selectively lacking CLEC-2 expression in dendritic cells. Thus, the same dendritic cells that initiate immunity by presenting antigens to T lymphocytes (3) also initiate remodelling of lymph nodes by delivering CLEC-2 to FRCs. CLEC-2 modulation of PDPN signalling permits FRC network stretching and allows for the rapid lymph node expansion--driven by lymphocyte influx and proliferation--that is the critical hallmark of adaptive immunity.<br />Lymph nodes are meeting places for T lymphocytes and antigen-presenting dendritic cells (1,2). T-cell-dendritic-cell interactions are supported by FRCs (4,5), a complex interconnected network that produces and ensheathes extracellular matrix [...]
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 514
- Issue :
- 7523
- Database :
- Gale General OneFile
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.388264109