The Deubiquitinating Modification Of IRF4 In Rheumatic Heart Disease

Background:Rheumatic heart disease is a serious chronic, autoimmune disease,it was caused by the beta hemolytic streptococcus.Rheumatic heart disease involving the heart, heart valves, even the pericardium.After a long period of inflammatory response, many people suffered hardships because of the damage of the heart. As it is reported that IL-4 increased in acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD), we’d like to study the mechanism by which the IL-4 increased, therefore try to provide some explanations for the development of RHD.Objective:To investigate the role of Ubiquitin-Specific Protease4 (USP4) in regulation of TH2 inmune response via Interferon Regulatory Factor 4 (IRF4) Deubiquitinating in Rheumatic Heart Disease (RHD), which provides a novel clinical potential target inprevention and treatment of RHD.Methods and Results:20 RHD patients were collected in our hospital, as control with 25 healthy individuals. The higher expression of USP4 was detected in RHD patients compared to healthy individuals by Real Time PCR and Immune Blot assay. We next screened several transcriptional factors which may be interacted with USP4 and further provided that IRF4 can interact and deubiquitinate with USP4 and then stabilize IRF4 in a dose dependent way. Furthermore, luciferase reporter assay proved that USP4 promote the transcription of IL-4 (indicating TH2 immune response)through interacting with IRF4 and NFATC2. In the end, Flow cytometry confirmed that the level of IRF4 and IL4 were higher regulated in RHD patients.Conclusion:Our study found a positive regulator of IRF4 which might be a potential therapeutic target for the treatment of RHD.