Tissue Expression And Mechanism Of MiRNAs In Response To Dexamethasone Affecting IBDV Immune Response In Chicken

Both stress-induced immunosuppression and infectious bursal disease（IBD）can suppress the body’s immune function.However,there is no report about the in vivo effect and mechanism of stress-induced immunosuppression affecting the immune response to IBDV vaccine.In this study,stress-induced immunosuppressed chickens were simulated with dexamethasone（dex）,and the expression characteristics and change rules of thirteen candidate IBDV-related serum circulating miRNAs at different time points were studied in the immunosuppressed chickens during the immune response to IBDV vaccine.In addition,the tissue expression characteristics and game relationships in vivo between miR-20a-5p and its predicted target gene BCL11 B at three-time points（2 days post immunization（dpi）,5dpi,21dpi）in different treatment groups were further studied.The main results of the study were as follows:Firstly,in dex-induced immunosuppressed chickens（Dex group）,the expression levels of serum circulating miR-106-5p,miR-146a-5p,miR-21-5p,miR-122-5p,miR-130b-3p and miR-20a-5p were significantly changed on 2dpi,5dpi,7dpi and 28 dpi.In the immune response to IBDV attenuated vaccine（IBD group）,serum circulating miR-21-5p,miR-20a-5p,miR-122-5p,miR-130b-3p and miR-6655-5p actively responded to the immune response on 2dpi,5dpi,7dpi,21 dpi,and 28 dpi.In stress-induced immunosuppression affecting the immune response to IBDV vaccine（Dex+IBD group）,2dpi,5dpi,7dpi and 28 dpi were the high-frequency change time points of serum circulating miR-16-5p,miR-21-5p,miR-122-5p,miR-142-5p and miR-6655-5p,and the expression trend of miR-20a-5p in the immune response were significantly affected by dex,so miR-20a-5p and its predicted target gene BCL11 B were selected as candidate targets for in-depth research.SeControldly,the expression characteristics of miR-20a-5p in eight tissues from different treatment groups were studied,respectively.In the Dex group,miR-20a-5p was significantly differentially expressed in the heart,thymus,glandular stomach and cecal tonsil.In the IBD group,miR-20a-5p was significantly differentially expressed in the bursa of Fabricius and cecal tonsils on 2 dpi and 21 dpi.In the Dex+IBD group,stress-induced immunosuppression might partially inhibit the effect of immune response to IBDV vaccine by regulating the expression activities of miR-20a-5p in the bursa of Fabricius,cecal tonsil,colon,and heart.Thirdly,the expression characteristics of BCL11 B gene in eight tissues from different treatment groups were also studied.In the Dex group,the BCL11 B gene was significantly differentially expressed in the spleen,bursa of Fabricius,thymus and cecal tonsil,and Dex might inhibit the proliferation of immune cells by up-regulating the expression of BCL11 B gene.In the IBD group,the expression levels of BCL11 B gene were generally lower and might be involved in the immune functions of the thymus and cecal tonsils.In the Dex+IBD group,stress-induced immunosuppression might partly inhibit the effect of immune response to IBDV vaccine by regulating the expression levels of BCL11 B gene in the thymus and cecal tonsils.Finally,the expression levels and game relationships between BCL11 B and miR-20a-5p on2 dpi,5dpi,and 21 dpi in different tissues from the Dex group,the IBD group,and the Dex+IBD group were analyzed comprehensively.The results showed that,in the Dex group,miR-20a-5p might be involved in the process of tissue development and immune cell proliferation affected by stress-induced immunosuppression by negatively regulating the expression of BCL11 B gene;in the IBD group,the miR-20a-5p-BCL11 B signal pathway might actively participate in the immune response in the spleen and bursa of Fabricius on 2dpi,while in the thymus and tonsils the high expression of BCL11 B on 21 dpi might be related to IBDV proliferation;in the Dex+IBD group,the immune response to IBDV vaccine might be suppressed by stress-induced immunosuppression by regulating the game relationships of miR-20a-5p-BCL11 B signal pathway in the heart,spleen,thymus and bursa of Fabricius.In this study,the expression characteristics of the candidate IBDV-related circulating miRNAs in serum were compared and analyzed,indicating that these circulating miRNAs were key factors that actively participated in stress-induced immunosuppression affecting the immune response to IBDV vaccine.Analysis of the tissue expression characteristics of miR-20a-5p and its predicted target gene BCL11 B showed that there were significant game relationships between miR-20a-5p and BCL11 B gene during the process of stress-induced immunosuppression affecting the immune response to IBDV vaccine in vivo.This study can provide a positive directional theoretical reference for in-depth studying the function and molecular mechanism of stress-induced immunosuppression affecting the IBDV immune response in vivo.