Dendritic cell SIRP regulates homeostasis of dendritic cells in lymphoid organs

Signal regulatory protein (SIRP), 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, SIRP is thought to be important for homeostasis of DCs, but it remains unclear whether SIRP intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRP was specifically ablated in CD11c(+) DCs (Sirpa(DC)). Sirpa(DC) mice manifested a marked reduction of CD4(+) CD8(-) conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa(DC) mice was comparable to that apparent with the mice, in which SIRP was systemically ablated. Expression of SIRP 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(DC) mice. Thus, our results suggest that SIRP intrinsic to CD11c(+) DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.