Control of myeloid cell density in barrier tissues

The interface between the mammalian host and its environment is formed by barrier tissues, for example, of the skin, and the respiratory and the intestinal tracts. On the one hand, barrier tissues are colonized by site-adapted microbial communities, and on the other hand, they contain specific myeloid cell networks comprising macrophages, dendritic cells, and granulocytes. These immune cells are tightly regulated in function and cell number, indicating important roles in maintaining tissue homeostasis and immune balance in the presence of commensal microorganisms. The regulation of myeloid cell density and activation involves cell-autonomous 'single-loop circuits' including autocrine mechanisms. However, an array of microenvironmental factors originating from nonimmune cells and the microbiota, as well as the microanatomical structure, impose additional layers of regulation onto resident myeloid cells. This review discusses models integrating these factors into cell-specific programs to instruct differentiation and proliferation best suited for the maintenance and renewal of immune homeostasis in the tissue-specific environment.