Bach2 keeps homeostasis in lung by regulating inflammatory response and maintaining function of alveolar macrophage [array]

Tissue resident macrophages show their specific function to maintain homeostasis in our body. Dysfunction of alveolar macrophages (AMs), which regulate the proper amount of surfactant protein, leads to the development of pulmonary alveolar proteinosis (PAP). Here we found that inflammation ruins the function of AMs and is one of the causes of secondary PAP. Inflammation leads to the loss of specific gene expression pattern of AMs and furthermore, it leads to gain the specific gene expression pattern of other tissue resident macrophages and DC lineage. We also found the critical roles for Bach2 expressed in AMs and T cells, whose expression is induced by IFNg released from T cells. Bach2 bounds to super-enhancer regions of the inflammatory genes of the myeloid lineage and represses excess inflammation in lungs. Our results suggest that Bach2 function among several cell lineages to modify the inflammation, maintaining homeostasis in lungs. Gene expression in alveolar macrophage from WT, Bach1 KO, Bach2 KO and Bach1/Bach2 DKO mouse was measured. 3 independent mice were used for each genotype.