Menin orchestrates macrophage reprogramming to maintain the pulmonary immune homeostasis
The potential importance of menin in immune regulation remains unclear. Here, we report that myeloid deletion of Men1 results in the development of spontaneous pulmonary alveolar proteinosis (PAP). This is strongly correlated with impaired development of alveolar macrophages (AM) and epigenetic inactivation of the GM-CSF pathway caused by Men1 deficiency. Mechanistically, menin directly interacts with SETD2 and collectively maintain GM-CSF expression through H3K36me3, which orchestrates AM reprogramming and pulmonary immune homeostasis. Overall design: Stimulation of BM-derived monocytes with M-CSF induced differentiation into pre-macrophages (BMDMs, M0). BMDM cells from WT(Men1f/f )and KO(Men1?M/?M) mice were harvested for ChIP-seq to determine the landscapes of menin, SETD2, H3K36me3 and H3K4me3 on chromatin