13:40 - 15:10
Room: ANA Crowne Plaza “Ohtori” Room A
Workshop Session
Chair/s:
Frederic Geissmann, Toshiaki Ohteki
SIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen
Yasuyuki Saito1, Satomi Komori1, Datu Respatika1, Ken Washio1, Takenori Kotani1, Yoji Murata1, Hiroshi Ohnishi2, Katsuyuki Yui3, Koji Yasutomo4, Takashi Matozaki1
1Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan, 2Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Japan, 3Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University,, Nagasaki, Japan, 4Department of Immunology and Parasitology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan

Stromal cells contribute to the structural organization of secondary lymphoid organs (SLOs) by producing cytokines and chemokines, which regulate the positioning and segregation of incoming dendritic cells (DCs) and T and B cells. We have previously shown that signal regulatory protein α (SIRPα) and its ligand CD47 are important for the homeostasis of type 2 conventional DCs (cDC2) that abundantly expresses SIRPα, as well as that of stromal cells such as podoplanin (Pdpn)–positive fibroblastic reticular cells (FRCs) in the spleen. The cellular and molecular basis for such regulation by SIRPα and CD47 has remained largely unclear, however. Here we showed that DC-specific ablation of SIRPα or CD47 (SirpaΔDC or Cd47ΔDC) markedly reduced the number of cDC2 as well as of Pdpn+ FRCs and T cells in the spleen. Such ablation also reduced CCL19 and CCL21 production and impaired the survival of FRCs in the spleen. In addition, the reduction in the number of cDC2 caused by tamoxifen-inducible ablation of SIRPα was followed by the consecutive depletion of FRCs and T cells in the spleen. By contrast, Irf4ΔDC and RbpjΔDC mice, both of which also impaired development and homeostasis of cDC2, did not manifest any reduction in the number of FRCs or T cells in the spleen. These results suggest that cDC2 maintain homeostasis of FRCs and SIRPα specifically regulates such function. Moreover, we found that the cDC2 promoted the proliferation or survival of stromal cells by producing TNFR ligands such as TNF-α. Indeed, the expression of Tnf mRNA was down-regulated in the CD4+ cDC2 subset sorted from SirpaΔDC or Cd47ΔDC mice. SIRPα+ cDC2 thus regulate the steady state homeostasis of FRCs in the adult spleen via the production of TNFR ligands, with the CD47-SIRPα interaction in cDC2 likely being indispensable for such regulation.


Reference:
We-WS13-4
Session:
Workshop 13, “Development and function of Macrophage and DC”
Presenter/s:
Yasuyuki Saito
Presentation type:
Oral Presentation
Room:
ANA Crowne Plaza “Ohtori” Room A
Chair/s:
Frederic Geissmann, Toshiaki Ohteki
Date:
Wednesday, 1 November 2017
Time:
14:22 - 14:34
Session times:
13:40 - 15:10