Détail du document
Identifiant
oai:pubmedcentral.nih.gov:1082...
Sujet
Original ArticleAuteur
Ji, Ningfei Chen, Zhongqi Wang, Zhengxia Sun, Wei Yuan, Qi Zhang, Xijie Jia, Xinyu Wu, Jingjing Jiang, Jingxian Song, Meijuan Xu, Tingting Liu, Yanan Ma, Qiyun Sun, Zhixiao Bao, Yanmin Zhang, Mingshun Huang, MaoLangue
enEditeur
The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
Catégorie
Allergy, Asthma & Immunology Research
Année
2023
Date de référencement
09/02/2024
Mots clés
triplex mice model pp2a + th2 differentiation asthma cd4 cellsRésumé
PURPOSE: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood.
We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma.
METHODS: LincR-PPP2R5C from RNA-seq data of CD4(+) T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH).
Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4(+) T cells.
The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer.
An ovalbumin-induced acute asthma model in knockout (KO) mice (LincR-PPP2R5C KO, CD4 conditional LincR-PPP2R5C KO) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation.
RESULTS: LncR-PPP2R5C was significantly higher in CD4(+) T cells from asthmatic mice ex vivo and Th2 cells in vitro.
The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation.
Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation.
The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A.
LincR-PPP2R5C KO and CD4 conditional KO decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses.
CONCLUSIONS: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma.
Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.
Ji, Ningfei,Chen, Zhongqi,Wang, Zhengxia,Sun, Wei,Yuan, Qi,Zhang, Xijie,Jia, Xinyu,Wu, Jingjing,Jiang, Jingxian,Song, Meijuan,Xu, Tingting,Liu, Yanan,Ma, Qiyun,Sun, Zhixiao,Bao, Yanmin,Zhang, Mingshun,Huang, Mao, 2023, LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming an RNA–DNA Triplex in Allergic Asthma, The Korean Academy of Asthma, Allergy and Clinical Immunology; The Korean Academy of Pediatric Allergy and Respiratory Disease
MELAS: Phenotype Classification into Classic-versus-Atypical Presentations
presentations mitochondrial strokelike patients variability phenotype clinical melas
