本文采用的英格恩产品: CCAA细胞凋亡检测试剂盒(PI)
A beneficial environment promotes immune resilience through epigenetic regulation
Affiliations
- 1 Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Munich, Germany.
- 2 Member of the German Center of Lung Research (DZL), Munich, Germany.
- 3 Institute for Asthma and Allergy Prevention, Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
- 4 Research Unit Precision Regenerative Medicine (PRM), Helmholtz Munich, Munich, Germany.
- 5 Institute of Network Biology (INET), Molecular Targets and Therapeutics Center (MTTC), Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
- 6 Department of Pharmacy, Center for Drug Research, Ludwig-Maximilian’s University, LMU, Munich, Germany.
- 7 Division of Lung Immunology, Priority Area Chronic Lung Diseases, Research Centre Borstel-Leibniz Lung Centre, Borstel, Germany.
- 8 Airway Research Center North, Member of the German Centre for Lung Research (DZL), Germany.
- 9 Institute for Immunology, Biomedical Center Munich, Faculty of Medicine, LMU Munich, Munich, Planegg-Martinsried, Germany.
- 10 Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Faculty of Medicine, LMU Munich, Munich, Germany.
- 11 Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-University Munich, Member of the German Center of Lung Research (DZL), Munich, Germany.
- 12 Microbe-Host Interactions, Faculty of Biology, Ludwig-Maximilians-Universität (LMU) München, Munich, Germany.
- 13 Institute of Experimental Pneumology, LMU University Hospital, Ludwig-Maximilian’s University, Munich, Germany.
- 14 Velocity Clinical Research Germany, Ahrensburg, Germany.
- 15 University of Lübeck, Airway Research Center North (ARCN), German Center for Lung Research (DZL), Lübeck, Germany.
- 16 Department of Pediatrics, Dr. von Hauner Children’s Hospital, LMU University Hospital, LMU Munich, Munich, Germany.
- PMID: 41758935
- PMCID: PMC12947861
- DOI: 10.1126/sciadv.ady7317
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.
