Brand, S.* ; Teich, R.* ; Dicke, T.* ; Harb, H.* ; Yildirim, A.Ö. ; Tost, J.* ; Schneider-Stock, R.* ; Waterland, R.A. * ; Bauer, U.M.* ; von Mutius, E.* ; Garn, H.* ; Pfefferle, P.I.* ; Renz, H.*
Epigenetic regulation in murine offspring as a novel mechanism for transmaternal asthma protection induced by microbes.
J. Allergy Clin. Immunol. 128, 618-625 (2011)
Background: Bronchial asthma is a chronic inflammatory disease resulting from complex gene-environment interactions. Natural microbial exposure has been identified as an important environmental condition that provides asthma protection in a prenatal window of opportunity. Epigenetic regulation is an important mechanism by which environmental factors might interact with genes involved in allergy and asthma development. Objective: This study was designed to test whether epigenetic mechanisms might contribute to asthma protection conferred by early microbial exposure. Methods: Pregnant maternal mice were exposed to the farm-derived gram-negative bacterium Acinetobacter lwoffii F78. Epigenetic modifications in the offspring were analyzed in T(H)1- and T(H)2-relevant genes of CD4(+) T cells. Results: Prenatal administration of A lwoffii F78 prevented the development of an asthmatic phenotype in the progeny, and this effect was IFN-gamma dependent. Furthermore, the IFNG promoter of CD4(+) T cells in the offspring revealed a significant protection against loss of histone 4 (H4) acetylation, which was closely associated with IFN-gamma expression. Pharmacologic inhibition of H4 acetylation in the offspring abolished the asthma-protective phenotype. Regarding T(H)2-relevant genes only at the IL4 promoter, a decrease could be detected for H4 acetylation but not at the IL5 promoter or the intergenic T(H)2 regulatory region conserved noncoding sequence 1 (CNS1). Conclusion: These data support the hygiene concept and indicate that microbes operate by means of epigenetic mechanisms. This provides a new mechanism in the understanding of gene-environment interactions in the context of allergy protection. (J Allergy Clin Immunol 2011;128:618-25.)
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Asthma; allergy; epigenetics; histone acetylation; hygiene hypothesis; T cells; ENCODING INTERFERON-GAMMA; GLOBAL GENE-EXPRESSION; NAIVE T-CELLS; DNA METHYLATION; AIRWAY HYPERRESPONSIVENESS; IGE PRODUCTION; DIFFERENTIATION; EXPOSURE; ALLERGY; INFLAMMATION
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2011
Prepublished im Jahr
HGF-Berichtsjahr
2011
ISSN (print) / ISBN
0091-6749
e-ISSN
1097-6825
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 128,
Heft: 3,
Seiten: 618-625
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
Amsterdam [u.a.]
Tag d. mündl. Prüfung
0000-00-00
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Gutachter
Prüfer
Topic
Hochschule
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Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Begutachtungsstatus
Peer reviewed
POF Topic(s)
30202 - Environmental Health
Forschungsfeld(er)
Lung Research
PSP-Element(e)
G-505000-007
Förderungen
Copyright
Erfassungsdatum
2011-11-10