Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses.

Details

Ressource 1Download: BIB_AE262022BADB.P001.pdf (3406.30 [Ko])
State: Public
Version: Final published version
Serval ID
serval:BIB_AE262022BADB
Type
Article: article from journal or magazin.
Collection
Publications
Title
Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses.
Journal
Journal of Experimental Medicine
Author(s)
Fasnacht N., Huang H.Y., Koch U., Favre S., Auderset F., Chai Q., Onder L., Kallert S., Pinschewer D.D., MacDonald H.R., Tacchini-Cottier F., Ludewig B., Luther S.A., Radtke F.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
2014
Volume
211
Number
11
Pages
2265-2279
Language
english
Abstract
Fibroblast-like cells of secondary lymphoid organs (SLO) are important for tissue architecture. In addition, they regulate lymphocyte compartmentalization through the secretion of chemokines, and participate in the orchestration of appropriate cell-cell interactions required for adaptive immunity. Here, we provide data demonstrating the functional importance of SLO fibroblasts during Notch-mediated lineage specification and immune response. Genetic ablation of the Notch ligand Delta-like (DL)1 identified splenic fibroblasts rather than hematopoietic or endothelial cells as niche cells, allowing Notch 2-driven differentiation of marginal zone B cells and of Esam(+) dendritic cells. Moreover, conditional inactivation of DL4 in lymph node fibroblasts resulted in impaired follicular helper T cell differentiation and, consequently, in reduced numbers of germinal center B cells and absence of high-affinity antibodies. Our data demonstrate previously unknown roles for DL ligand-expressing fibroblasts in SLO niches as drivers of multiple Notch-mediated immune differentiation processes.
Keywords
Notch soignaling, TFH
Pubmed
Web of science
Open Access
Yes
Create date
30/10/2014 17:38
Last modification date
20/08/2019 16:17
Usage data