Publikation
Specific fibroblastic niches in secondary lymphoid organs orchestrate distinct Notch-regulated immune responses
Wissenschaftlicher Artikel/Review - 13.10.2014
Fasnacht Nicolas, Luther Sanjiv A, Ludewig Burkhard, Tacchini-Cottier Fabienne, MacDonald H Robson, Pinschewer Daniel D, Kallert Sandra, Onder Lucas, Chai Qian, Auderset Floriane, Favre Stéphanie, Koch Ute, Huang Hsin-Ying, Radtke Freddy
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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.