It has been known that an increase of brain immune cells expressing CD11c, which is a dendric cell (DC) marker, occurs commonly in the aged and inflamed brain. However, the pathological or physiological significance of CD11c-positive cells in such states of the brain is not fully understood. Signal regulatory protein α (SIRP α ), an immunoglobulin superfamily (IgSF) membrane protein that is predominantly expressed in DC or macrophages in the immune system, mediates cell-cell communication signal by interacting with CD47, another IgSF membrane protein. In the central nervous system, both SIRP α and CD47 are predominantly expressed in neurons. SIRP α is also expressed in microglia, while roles of the CD47-SIRP α signal in regulation of microglial cell functions remain unclear. We found that genetic ablation of SIRP α induced an increase in the number of cells that expressed CD11c in the brain of SIRP α knockout mice. These brain CD11c-positive (bCD11c⁺) cells expressed microglial marker proteins, CD11b and Iba-1. In addition, the expression level of CD45, a marker protein for hematopoietic cells, was intermediate or low in the bCD11c⁺ cells. These results suggest that the bCD11c⁺ cells belong to a subpopulation of brain-resident microglia. These bCD11c⁺ microglia also expressed CD14 or Dectin-1, cell surface receptors characteristically expressed on cells that contribute to induction of the innate immune response. An increase in the number of the bCD11c⁺ microglia was also observed in CD47 KO mice, suggesting that lack of the interaction between CD47 and SIRP α resulted in the same phenotype. Although the cell types that are mainly involved in the CD47-SIRP α signal and thus control the number of bCD11c⁺ microglia remains to be defined, intercellular interaction mediated by CD47 and SIRP α is critical to maintain homeostasis of brain microglia.