The local signals leading to the diversity of tissue-resident macrophages remain largely unknown. Together, the findings of two studies now show that peritoneal-specific signals reversibly induce activation of the transcription factor GATA6 in resident macrophages, which regulates their phenotype and localization in the peritoneum and helps resolve inflammation at this site. The findings highlight the need for tissue-derived signals to induce plasticity of tissue macrophages and adapt to environmental changes (Cell 157, 832–844, 2014 and Science 344, 645–648, 2014).
By comparing mouse macrophages from different tissues, Yasutaka Okabe and Ruslan Medzhitov found GATA6 highly expressed in peritoneal macrophages and responsible for regulating their localization in the peritoneal cavity. The authors identified retinoic acid (found in the fat tissue associated with the peritoneum) as the upstream local signal that activates Gata6 as well as other peritoneal macrophage–specific genes. Mice lacking vitamin A, a precursor of retinoic acid, had a smaller number of peritoneal macrophages and lower expression of Gata6 and other specific genes, confirming the role of this axis in inducing this gene expression program and in maintaining these macrophages at this location, which helped ameliorate inflammation. Functionally, activation of GATA6 by retinoic acid in these macrophages regulated the production of IgA by peritoneal B-1 immune cells.
This is a preview of subscription content, access via your institution