A beneficial environment promotes immune resilience through epigenetic regulation

Environmental factors are often detrimental; however, certain environments enhance immune resilience. Notably, children raised on traditional farms show reduced allergies and asthma prevalence. Here, we investigated how a beneficial environment, using farm dust (FD) extract, influenced lung immune function in OVA-induced allergic inflammation. FD-exposure reduced allergic lung inflammation and increased monocyte-derived macrophage (MDM) recruitment. scRNA-seq revealed that FD-exposed MDMs had altered gene expression, including dampened Ccl8 and MHCII expression, impairing eosinophil recruitment and antigen presentation. RNA-seq and ATAC-seq confirmed FD-induced epigenetic reprogramming ex-vivo, on bone marrow-derived macrophages. This modulation, seen in both human and murine cells, relied on HDAC activity sustained by PPAR? signaling. These findings suggest that beneficial environmental exposures can reprogram immune cells and may offer a novel strategy for asthma prevention. Overall design: ATAC-seq profiling of mouse BMDM and BMDC treated with 100 µg/ml FD or PBS twice over a 24-hour period then incubated with 10 ng/ml LPS for 6 hours