A beneficial environment promotes immune resilience through epigenetic regulation

Sci Adv. 2026 Feb 27;12(9):eady7317. doi: 10.1126/sciadv.ady7317. Epub 2026 Feb 27.

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.

MeSH terms

  • Animals
  • Asthma / genetics
  • Asthma / immunology
  • Dust / immunology
  • Environmental Exposure
  • Epigenesis, Genetic*
  • Humans
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Ovalbumin
  • PPAR gamma / metabolism

Substances

  • Dust
  • Ovalbumin
  • PPAR gamma