Cornelia de Lange综合征(Cornelia de Lange syndrome,CdLS)在1933年由荷兰儿科医生Cornelia首次描述,该病是一种伴有多系统发育异常的遗传缺陷综合征,呈常染色体显性或X连锁显性方式遗传,发病率介于1/10000~1/30000活产新生儿,常表现...Cornelia de Lange综合征(Cornelia de Lange syndrome,CdLS)在1933年由荷兰儿科医生Cornelia首次描述,该病是一种伴有多系统发育异常的遗传缺陷综合征,呈常染色体显性或X连锁显性方式遗传,发病率介于1/10000~1/30000活产新生儿,常表现为成比例的身材矮小、宫内及出生后发育迟缓、特定的面部特征、多器官系统畸形(特别是心脏、胃肠道和肌肉骨骼系统)以及认知和行为方面的异常等。该病常见的突变基因有NIPBL、SMC1A、SMC3、RAD21、BRD4、HDAC8和ANKRD11,所有这些基因表达的蛋白都参与组成黏连蛋白复合物或影响其调节功能[1-2]。本团队对1例CdLS患儿及其家系成员进行基因突变检测,发现患儿携带HDAC8基因c.111+3A>T新发突变,既往未见报道,并统计中国目前报道的HDAC8基因突变所致CdLS患者基因型及临床表现,具体报告如下。展开更多
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
文摘Cornelia de Lange综合征(Cornelia de Lange syndrome,CdLS)在1933年由荷兰儿科医生Cornelia首次描述,该病是一种伴有多系统发育异常的遗传缺陷综合征,呈常染色体显性或X连锁显性方式遗传,发病率介于1/10000~1/30000活产新生儿,常表现为成比例的身材矮小、宫内及出生后发育迟缓、特定的面部特征、多器官系统畸形(特别是心脏、胃肠道和肌肉骨骼系统)以及认知和行为方面的异常等。该病常见的突变基因有NIPBL、SMC1A、SMC3、RAD21、BRD4、HDAC8和ANKRD11,所有这些基因表达的蛋白都参与组成黏连蛋白复合物或影响其调节功能[1-2]。本团队对1例CdLS患儿及其家系成员进行基因突变检测,发现患儿携带HDAC8基因c.111+3A>T新发突变,既往未见报道,并统计中国目前报道的HDAC8基因突变所致CdLS患者基因型及临床表现,具体报告如下。
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.
