Two Distinct Subsets Are Identified from the Peritoneal Myeloid Mononuclear Cells Expressing both CD11c and CD115

To this date, the criteria to distinguish peritoneal macrophages and dendritic cells (DCs) are not clear. Here we delineate the subsets of myeloid mononuclear cells in the mouse peritoneal cavity. Considering phenotypical, functional, and ontogenic features, peritoneal myeloid mononuclear cells are divided into 5 subsets: large peritoneal macrophages (LPMs), small peritoneal macrophages (SPMs), DCs, and 2 MHCII⁺CD11c⁺CD115⁺ subpopulations (i.e., MHCII⁺CD11c⁺CD115⁺CD14^-CD206^- and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺). Among them, 2 subsets of competent Ag presenting cells are demonstrated with distinct functional characteristics, one being DCs and the other being MHCII⁺CD11c⁺CD115⁺CD14^-CD206^- cells. DCs are able to promote fully activated T cells and superior in expanding cytokine producing inflammatory T cells, whereas MHCII⁺CD11c⁺CD115⁺CD14^-CD206^- cells generate partially activated T cells and possess a greater ability to induce Treg under TGF-β and retinoic acid conditions. While the development of DCs and MHCII⁺CD11c⁺CD115⁺CD14^-CD206^- cells are responsive to the treatment of FLT3 ligand and GM-CSF, the number of LPMs, SPMs, and MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells are only influenced by the injection of GM-CSF. In addition, the analysis of gene expression profiles among MHCII⁺ peritoneal myeloid mononuclear cells reveals that MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells share high similarity with SPMs, whereas MHCII⁺CD11c⁺CD115⁺CD14^-CD206^- cells are related to peritoneal DC2s. Collectively, our study identifies 2 distinct subpopulations of MHCII⁺CD11c⁺CD115⁺ cells, 1) MHCII⁺CD11c⁺CD115⁺CD14^-CD206^- cells closely related to peritoneal DC2s and 2) MHCII⁺CD11c⁺CD115⁺CD14⁺CD206⁺ cells to SPMs.