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

Fasnacht, Nicolas and Huang, Hsin-Ying and Koch, Ute and Favre, Stéphanie and Auderset, Floriane and Chai, Qian and Onder, Lucas and Kallert, Sandra and Pinschewer, Daniel D. and MacDonald, H. Robson and Tacchini-Cottier, Fabienne and Ludewig, Burkhard and Luther, Sanjiv A. and Radtke, Freddy. (2014) Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses. The Journal of experimental medicine, 211 (11). pp. 2265-2279.

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Official URL: https://edoc.unibas.ch/61978/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Jul 2020 14:49
Deposited On:27 Jul 2020 14:49

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