A beneficial environment promotes immune resilience through epigenetic regulation

INET

Dragunas, G., Klotz, M., Chen, S., Ertüz, Z., Tan, X., Korkmaz, Ü. R., Shankhwar, S., Rankl, B., Dhakad, D., Omony, J., Mayr, C. H., Chen, Y., Agami, A., Lin, C. W., Müller, C., Lunding, L., Wegmann, M., Berner, J., Popovic, J., Schraml, B. U., Adler, H., Falter-Braun, P., Schiller, H., Watz, H., Conlon, T. M., Jeridi, A., Kapellos, T. S., von Mutius, E. & Yildirim, A. Ö. A beneficial environment promotes immune resilience through epigenetic regulation. Sci. Adv. 12, eady7317 (2026).

Abstract

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.