Tissue-specific control of macrophage phenotype and its relevance to inflammation

Tissue resident macrophages are a highly heterogeneous cell type present in every mammalian tissue, where they have a critical role in innate immune defence and tissue homeostasis. Tissue-specific master regulators have been identified in different tissue-resident macrophage populations, which regulate macrophage tissue-specific phenotype and function through the induction and maintenance of specific transcriptional programs. However, it is largely unclear how transcriptional master regulators control tissue-specific macrophage phenotype during the initiation of the inflammatory response and the resolution thereof. Genetic deletion of these tissue-specific transcriptional regulators typically results in the ablation of the specific macrophage populations, such as the loss of splenic red pulp macrophages in of Spi-C deficient mice. Conversely, genetic deletion of Gata6 in macrophages does not completely ablate the population of peritoneal macrophages, albeit it leaves them at reduced numbers. Thus, Gata6-deficient pMϕs provide a unique tool to investigate how tissue-specific transcription factors regulate macrophage function during homeostasis and in response to environmental stimuli