PT  - JOURNAL ARTICLE
AU  - C. Mirella Spalluto
AU  - Akul Singhania
AU  - Christopher H. Woelk
AU  - Tilman Sanchez-Elsner
AU  - Karl J. Staples
AU  - Tom M.A. Wilkinson
TI  - IFNγ influences bronchial epithelial anti-viral immune responses via inducible epigenetic control of histone methylation of the RIG-I promoter
AID  - 10.1183/13993003.congress-2015.OA1782
DP  - 2015 Sep 01
TA  - European Respiratory Journal
PG  - OA1782
VI  - 46
IP  - suppl 59
4099  - http://erj.ersjournals.com/content/46/suppl_59/OA1782.short
4100  - http://erj.ersjournals.com/content/46/suppl_59/OA1782.full
SO  - Eur Respir J2015 Sep 01; 46
AB  - Environmental exposures in the neonatal period including severe viral infections are linked to the development of asthma. During early life, the adaptive immune system undergoes rapid maturation from a tolerant (Th2) to an anti-infective (Th1) mode. The inability to produce adequate IFNγ at birth may lead to increased asthma susceptibility. Our aim was to investigate whether the inflammatory environment of the airway epithelium epigenetically modulates the expression of anti-viral genes leading to long term abnormalities such asthma.We infected AALEB, a human immortalised bronchial epithelial cell line, with RSV in the presence or absence of IFNγ or IL-13. Microarray analysis identified a 2.4 fold increase in the viral sensor RIG-I mRNA in IFNγ primed cells compared to un-primed(p=0.006), associated with a 2.55 fold reduction in RSV replication (p=0.041). We investigated the role of histone modifications in RIG-I transcription by ChIP. IFNγ priming induced a 3 fold reduction of the repressive marker H3K9me3 (p=0.029) that was associated with a 4.2 fold increase in RIG-I mRNA (p=0.016). The methyltransferase inhibitor BIX-01294 significantly enhanced RIG-I transcription of primed cells by 50% (p=0.039) suggesting an involvement of lysine methyltransferase in RIG-I epigenetic regulation.This in-vitro study suggests that modulating the inflammatory environment of naive epithelial cells can induce epigenetic changes in innate immune responses at the level of histone methylation. This could potentially lead to long term impacts on anti-viral immunity. The presence of a Th1 milieu appears key to the development of effective anti-viral responses.