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 ovalbumin-induced allergic inflammation. FD exposure reduced allergic lung inflammation and increased monocyte-derived macrophage (MDM) recruitment. Single-cell RNA sequencing revealed that FD-exposed MDMs had altered gene expression, including dampened Ccl8 and major histocompatibility complex class II expression, impairing eosinophil recruitment and antigen presentation. RNA sequencing and assay for transposase-accessible chromatin using sequencing confirmed FD-induced epigenetic reprogramming ex vivo, on bone marrow-derived macrophages. This modulation, seen in both human and murine cells, relied on histone deacetylase activity sustained by peroxisome proliferator-activated receptor γ signaling. These findings suggest that beneficial environmental exposures can reprogram immune cells and may offer a previously unidentified strategy for asthma prevention.