Background:Dendritic cells(DCs)play a pivotal role in antigen presentation and regulating adaptive immune responses in asthma pathophysiology.However,the underlying molecular mechanisms remain incompletely understood....Background:Dendritic cells(DCs)play a pivotal role in antigen presentation and regulating adaptive immune responses in asthma pathophysiology.However,the underlying molecular mechanisms remain incompletely understood.Methods:Bioinformatics analysis of the GSE27011 dataset identified differentially expressed genes associated with pediatric asthma.An ovalbumin(OVA)-induced asthma mouse model and an Rfx5 knockdown model were established.RFX5 expression was assessed in DCs from patients with asthma and asthmatic mouse lung tissues using qRT-PCR,Western blotting,and immunohistochemistry.The regulatory effects of regulatory factor X5(RFX5)on histone deacetylase 2(HDAC2),class II major histocompatibility complex transactivator(CIITA),and major histocompatibility complex class II molecules(MHC II)expression,as well as its influence on lung tissue integrity,airway resistance,cytokine profiles,and immune cell infiltration,were analyzed.Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to explore the interaction between RFX5 and HDAC2.Results:During asthma progression,RFX5 expression was upregulated,while HDAC2 levels were reduced in DCs.Rfx5 knockdown significantly alleviated lung pathology and inflammation,decreased granulocyte and lymphocyte counts,and lowered levels of pro-inflammatory cytokines interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1β(IL-1β).In contrast,the expression of anti-inflammatory cytokines such as interleukin 4(IL-4),interleukin 10(IL-10),interleukin 18(IL-18),and prostaglandin E2(PGE2)was elevated,along with an increase in CIITA and MHC II gene transcription.Further analysis revealed a direct association between HDAC2 and the RFX5 promoter region.Conclusion:During asthma pathogenesis,allergens may upregulate RFX5 expression in DCs,enhancing its interaction with HDAC2,thereby alleviating the HDAC2-mediated effect.This process promotes the transcription of MHC II-associated genes and facilitates antigen presentation,ultimately driving asthma initiation and progression.This study elucidates the role of the RFX5/HDAC2 signaling pathway in the regulation of antigen presentation in pediatric asthma.展开更多
基金supported by the 2021 Jiangxi Provincial Department of Science and Technology Applied Research Cultivation Plan Project(No.20212BAG70005,Yahui Wu)2021 Science and Technology Special Project and Social Development Project in Ji’an City,Jiangxi Province(No.20211-025242,Yahui Wu).
文摘Background:Dendritic cells(DCs)play a pivotal role in antigen presentation and regulating adaptive immune responses in asthma pathophysiology.However,the underlying molecular mechanisms remain incompletely understood.Methods:Bioinformatics analysis of the GSE27011 dataset identified differentially expressed genes associated with pediatric asthma.An ovalbumin(OVA)-induced asthma mouse model and an Rfx5 knockdown model were established.RFX5 expression was assessed in DCs from patients with asthma and asthmatic mouse lung tissues using qRT-PCR,Western blotting,and immunohistochemistry.The regulatory effects of regulatory factor X5(RFX5)on histone deacetylase 2(HDAC2),class II major histocompatibility complex transactivator(CIITA),and major histocompatibility complex class II molecules(MHC II)expression,as well as its influence on lung tissue integrity,airway resistance,cytokine profiles,and immune cell infiltration,were analyzed.Co-immunoprecipitation and chromatin immunoprecipitation assays were performed to explore the interaction between RFX5 and HDAC2.Results:During asthma progression,RFX5 expression was upregulated,while HDAC2 levels were reduced in DCs.Rfx5 knockdown significantly alleviated lung pathology and inflammation,decreased granulocyte and lymphocyte counts,and lowered levels of pro-inflammatory cytokines interleukin 6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1β(IL-1β).In contrast,the expression of anti-inflammatory cytokines such as interleukin 4(IL-4),interleukin 10(IL-10),interleukin 18(IL-18),and prostaglandin E2(PGE2)was elevated,along with an increase in CIITA and MHC II gene transcription.Further analysis revealed a direct association between HDAC2 and the RFX5 promoter region.Conclusion:During asthma pathogenesis,allergens may upregulate RFX5 expression in DCs,enhancing its interaction with HDAC2,thereby alleviating the HDAC2-mediated effect.This process promotes the transcription of MHC II-associated genes and facilitates antigen presentation,ultimately driving asthma initiation and progression.This study elucidates the role of the RFX5/HDAC2 signaling pathway in the regulation of antigen presentation in pediatric asthma.
