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 gamma signaling. These findings suggest that beneficial environmental exposures can reprogram immune cells and may offer a previously unidentified strategy for asthma prevention.
- Dragunas, G.
- Klotz, M.
- Chen, S.
- Ertuz, Z.
- Tan, X.
- Korkmaz, U. R.
- Shankhwar, S.
- Rankl, B.
- Dhakad, D.
- Omony, J.
- Mayr, C. H.
- Chen, Y.
- Agami, A.
- Lin, C. W.
- Muller, 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. O.
