Fibroblastic reticular cell response to dendritic cells requires coordinated activity of podoplanin, CD44 and CD9

被引:13
作者
de Winde, Charlotte M. [1 ,2 ]
Makris, Spyridon [1 ]
Millward, Lindsey J. [1 ]
Cantoral-Rebordinos, Jesus A. [1 ]
Benjamin, Agnesska C. [1 ]
Martinez, Victor G. [1 ,3 ]
Acton, Sophie E. [1 ]
机构
[1] UCL, MRC Lab Mol Cell Biol, Stromal Immunol Grp, Gower St, London WC1E 6BT, England
[2] Amsterdam UMC, Dept Mol Cell Biol & Immunol, Locat VUrnc, De Boelelaan 1108, NL-1081 HZ Amsterdam, Netherlands
[3] CIEMAT, Mol Oncol Unit, Av Complutense 40, Madrid 28040, Spain
基金
欧洲研究理事会; 英国医学研究理事会;
关键词
Fibroblastic reticular cell; Lymph node; Podoplanin; CD44; CD9; Tetraspanins; Dendritic cell; LYMPHOID STROMA; NETWORKS; MOTILITY; CLEC-2; RHOA;
D O I
10.1242/jcs.258610
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In adaptive immunity, CLEC-2(+) dendritic cells (DCs) contact fibroblastic reticular cells (FRCs) inhibiting podoplanin-dependent actomyosin contractility, permitting FRC spreading and lymph node expansion. The molecular mechanisms controlling lymph node remodelling are incompletely understood. We asked how podoplanin is regulated on FRCs in the early phase of lymph node expansion, and which other proteins are required for the FRC response to DCs. We find that podoplanin and its partner proteins CD44 and CD9 are differentially expressed by specific lymph node stromal populations in vivo, and their expression in FRCs is coregulated by CLEC-2 (encoded by CLEC1B). Both CD44 and CD9 suppress podoplanin-dependent contractility. We find that beyond contractility, podoplanin is required for FRC polarity and alignment. Independently of podoplanin, CD44 and CD9 affect FRC-FRC interactions. Furthermore, our data show that remodelling of the FRC cytoskeleton in response to DCs is a two-step process requiring podoplanin partner proteins CD44 and CD9. Firstly, CLEC-2 and podoplanin binding inhibits FRC contractility, and, secondly, FRCs form protrusions and spread, which requires both CD44 and CD9. Together, we show a multi-faceted FRC response to DCs, which requires CD44 and CD9 in addition to podoplanin.
引用
收藏
页数:14
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