TFEB regulates dendritic cell antigen presentation to modulate immune balance in asthma

被引：5

作者：

Xiang, Jinying ^{[1
]}

Liu, Bo ^{[2
]}

Li, Yan ^{[1
]}

Ren, Yinying ^{[1
]}

Li, Yuehan ^{[1
]}

Zhou, Mi ^{[1
]}

Yu, Jinyue ^{[3
,4
]}

Luo, Zhengxiu ^{[1
]}

Liu, Enmei ^{[1
]}

Fu, Zhou ^{[1
]}

Ding, Fengxia ^{[1
]}

机构：

[1] Chongqing Med Univ, Chongqing Engn Res Ctr Stem Cell Therapy, Natl Clin Res Ctr Child Hlth & Disorders, Dept Resp Med,Minist Educ,Key Lab Child Dev & Diso, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China

[2] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Int Sci & Technol Cooperat Base Child Dev & Crit D, Dept Surg Oncol,Childrens Hosp,Minist Educ,Key Lab, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China

[3] Univ Bristol, Bristol Med Sch, Bristol, England

[4] UCL, Great Ormond St Inst Child Hlth, London, England

来源：

RESPIRATORY RESEARCH | 2024年 / 25卷 / 01期

关键词：

TFEB; Dendritic cell; Asthma; Antigen presentation; T cell; DIFFERENTIATION; ACTIVATION; EXPRESSION; SUBSETS; TYPE-2;

D O I：

10.1186/s12931-024-02806-1

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

ObjectiveAsthma stands as one of the most prevalent chronic respiratory conditions in children, with its pathogenesis tied to the actived antigen presentation by dendritic cells (DCs) and the imbalance within T cell subgroups. This study seeks to investigate the role of the transcription factor EB (TFEB) in modulating the antigen presentation process of DCs and its impact on the differentiation of T cell subgroups.MethodsBone marrow dendritic cells (BMDCs) were activated using house dust mites (HDM) and underwent RNA sequencing (RNA-seq) to pinpoint differentially expressed genes. TFEB mRNA expression levels were assessed in the peripheral blood mononuclear cells (PBMCs) of both healthy children and those diagnosed with asthma. In an asthma mouse model induced by HDM, the TFEB expression in lung tissue DCs was evaluated. Further experiments involved LV-shTFEB BMDCs co-cultured with T cells to explore the influence of TFEB on DCs' antigen presentation, T cell subset differentiation, and cytokine production.ResultsTranscriptomic sequencing identified TFEB as a significantly differentially expressed gene associated with immune system pathways and antigen presentation. Notably, TFEB expression showed a significant increase in the PBMCs of children diagnosed with asthma compared to healthy counterparts. Moreover, TFEB exhibited heightened expression in lung tissue DCs of HDM-induced asthmatic mice and HDM-stimulated BMDCs. Silencing TFEB resulted in the downregulation of MHC II, CD80, CD86, and CD40 on DCs. This action reinstated the equilibrium among Th1/Th2 and Th17/Treg cell subgroups, suppressed the expression of pro-inflammatory cytokines like IL-4, IL-5, IL-13, and IL-17, while augmenting the expression of the anti-inflammatory cytokine IL-10.ConclusionTFEB might have a vital role in asthma's development by impacting the antigen presentation of DCs, regulating T cell subgroup differentiation, and influencing cytokine secretion. Its involvement could be pivotal in rebalancing the immune system in asthma. These research findings could potentially unveil novel therapeutic avenues for treating asthma.

引用

页数：17