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Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):E10151-E10160. doi: 10.1073/pnas.1711345114. Epub 2017 Nov 6.

SIRPα+ dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen.

Author information

1
Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; ysaito@med.kobe-u.ac.jp matozaki@med.kobe-u.ac.jp.
2
Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
3
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
4
Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, Maebashi, Gunma 371-8514, Japan.
5
Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
6
Division of Immunology, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.
7
Department of Immunology and Parasitology, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima 770-8503, Japan.

Abstract

In secondary lymphoid organs, development and homeostasis of stromal cells such as podoplanin (Pdpn)-positive fibroblastic reticular cells (FRCs) are regulated by hematopoietic cells, but the cellular and molecular mechanisms of such regulation have remained unclear. Here we show that ablation of either signal regulatory protein α (SIRPα), an Ig superfamily protein, or its ligand CD47 in conventional dendritic cells (cDCs) markedly reduced the number of CD4+ cDCs as well as that of Pdpn+ FRCs and T cells in the adult mouse spleen. Such ablation also impaired the survival of FRCs as well as the production by CD4+ cDCs of tumor necrosis factor receptor (TNFR) ligands, including TNF-α, which was shown to promote the proliferation and survival of Pdpn+ FRCs. CD4+ cDCs thus regulate the steady-state homeostasis of FRCs in the adult spleen via the production of TNFR ligands, with the CD47-SIRPα interaction in cDCs likely being indispensable for such regulation.

KEYWORDS:

CD47; dendritic cell; fibroblastic reticular cell; signal regulatory protein α; tumor necrosis factor-α

PMID:
29109283
PMCID:
PMC5703302
DOI:
10.1073/pnas.1711345114
[Indexed for MEDLINE]
Free PMC Article

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