Modulation of infiltrating CD206-positive macrophages restricts progression of pulmonary lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is a very rare disease affecting women of childbearing age, either sporadically or in association with tuberous sclerosis complex (TSC). The proliferation of TSC2 null LAM cells in the lung results in cystic destruction, airflow obstruction, respiratory insufficiency and eventually death. In the LAM lung, the tumor immune microenvironment (TME) plays a role in the progression of LAM lesions. Macrophages can be polarized into inflammatory M1 macrophages or protumorigenic immunosuppressive M2 macrophages. Macrophages are an important component of the TME, and we hypothesized that CD206+ M2 macrophages could facilitate LAM progression and represent a potential therapeutic target. Overall design: To study the effect of TSC2 null cells on the macrophage polarization, we cocultured RAW264.7 macrophages with Tsc2-null TTJ cells derived from an angiomyolipoma of a murine model of tuberous sclerosis complex. We perfomed gene expression analysis using RNA-seq data from FACS-sorted control RAW264.7 cells or RAW264.7 cells cocultured for 48h with TTJ cells.