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

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 ? (SIRP?), 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-?, 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-SIRP? interaction in cDCs likely being indispensable for such regulation.

SUBMITTER: Saito Y 

PROVIDER: S-EPMC5703302 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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

Saito Yasuyuki Y   Respatika Datu D   Komori Satomi S   Washio Ken K   Nishimura Taichi T   Kotani Takenori T   Murata Yoji Y   Okazawa Hideki H   Ohnishi Hiroshi H   Kaneko Yoriaki Y   Yui Katsuyuki K   Yasutomo Koji K   Nishigori Chikako C   Nojima Yoshihisa Y   Matozaki Takashi T  

Proceedings of the National Academy of Sciences of the United States of America 20171106 47

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<sup>+</sup> cDCs as well as that of Pd  ...[more]