Foxp3 promoter methylation impairs suppressive function of regulatory T cells in biliary atresia

Kang Li, Xi Zhang, Li Yang, Xin-xing Wang, De-hua Yang, Guo-qing Cao, Shuai Li, Yong-zhong Mao, Shao-tao Tang
2016 American Journal of Physiology - Gastrointestinal and Liver Physiology  
BA) is characterized by progressive inflammation of the biliary system leading to liver cirrhosis, necessitating liver transplantation in pediatric patients. Various cell types have been reported to participate in the proinflammatory response in rhesus rotavirus (RRV)-induced BA mouse models, including T helper (Th) 1, Th2, Th17, CD8 ϩ T cells, and natural killer cells. The immune suppressive regulatory T (Treg) cells, on the contrary, were reported not to function properly. The underlying
more » ... The underlying mechanism is largely unknown. Focusing on the impaired suppressive function of Treg, we found methylation status of CpG islands within the Foxp3 promoter region of Treg cells in BA patients and murine models were both increased. Moreover, by injecting 5-aza-2=-deoxycytidine (Aza) as DNA-methylation inhibitor to RRVinfected mice, BA phenotypes were alleviated. Furthermore, Treg cells isolated from "RRVϩAza"-injected mice had better suppressive function than Treg cells from mice injected with RRV only, both in vivo and ex vivo. Thus we concluded that aberrant increased methylation status of "Foxp3 promoter" in Treg cells leads to impaired Treg suppressive function, exacerbating inflammatory injury in BA.
doi:10.1152/ajpgi.00032.2016 pmid:27659419 fatcat:ijmdqa5shbefrnegp7l3bl2pcu