No abstract

Because cholinergic urticaria is not a homogeneous disease, its subtype classification is essential for selection of the most suitable therapeutic method.

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.

Signal regulatory protein a (SIRPa), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell-cell signaling. In the immune system, SIRPa is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPa intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPa was specifically ablated in CD11c + DCs (Sirpa DDC ). Sirpa DDC mice manifested a marked reduction of CD4 + CD8a -conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa DDC mice was comparable to that apparent with the mice, in which SIRPa was systemically ablated. Expression of SIRPa in DCs was well correlated with that of either endothelial cell-selective adhesion molecule (ESAM) or Epstein-Barr virus-induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM + or EBI2 + cDCs were markedly reduced in the spleen of Sirpa DDC mice. Thus, our results suggest that SIRPa intrinsic to CD11c + DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.