IQUIBICEN   23947
INSTITUTO DE QUIMICA BIOLOGICA DE LA FACULTAD DE CIENCIAS EXACTAS Y NATURALES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
- hCG regulates IP-10 expression through histone methylation on in human endometrial stromal cells.
Autor/es:
Y. YANG-HARTWICH, R. RAMHORST, E. GRASSO,S. DUROSIER, P ALDO, G. MOR
Lugar:
Maryland
Reunión:
Congreso; 36th Meeting of the American Society for Reproductive Immunology; 2016
Institución organizadora:
The American Society for Reproductive Immunology
Resumen:
Problem : Human chorionic gonadotropin (hCG) is an immune regulatorprevenng T- cell migraon and acvaon. The decidua plays amajor role in immune cell migraon, especially T- cell migraon. IP- 10is a major T- cell chemoaractant, and elevated levels due to infec-on are associated with adverse pregnancy outcomes. However, themechanism that regulates chemokines and immune cell migraon inthe decidua is unknown. Studies suggest that epigenec regulaon isan important immune mechanism. The PRC2 complex (of which EZH2is the funconal enzyme) is the main protein complex regulang histonemethylaon, which silences target genes by binding to DNA. Wehypothesize that hCG immune regulaon occurs by chemokine repressionin the decidua. In this study we demonstrate that hCG, through thePRC2 complex, enhances histone methylaon (resulng in H3K27me3),which then binds to a specific locaon in the promoter of IP- 10, repressingIP- 10 expression. Modificaons in histone methylaon can decreasehistone binding, leading to IP- 10 expression and pregnancy loss.Method of Study : In vitro studies were done using the human endometrialstromal cell line (hESC). IP- 10 and EZH2 expression were determinedby quantave PCR and WB analysis. T- cell migraon assayswere performed using the two- chamber migraon assay comparingcondioned media from stromal cells and decidualized stromal cells.Chroman immunoprecipitaon was performed to determine thebinding region of H3K27me3 by PCR. Organ cultures were preparedfrom freshly isolated human decidua ssue (non labor). Expressionand secreon of IP- 10 in decidua ssue was determined by quanta-ve PCR and ELISA.Results : hCG- inhibits IP- 10 expression by inducing H3K27me3 histonemethylaon, which binds to Region 4 (505?601 bp upstream)of the IP- 10 promoter, thereby suppressing IP- 10 expression. hCGinducedhistone methylaon is through EZH2, the major funconalmember of the PRC2 complex. T- cell migraon is decreased towardscondioned media from decidualized stromal cells compared to nondecidualizedstromal cells. LPS treatment reverses the hCG inhibitoryeffect increasing IP- 10 expression/secreon and enhancing therecruitment of CD8+ cells. These findings were validated using anorgan culture of freshly isolated human decidua ssue.