PMID- 38262392
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240220
IS  - 2092-7355 (Print)
IS  - 2092-7363 (Electronic)
IS  - 2092-7355 (Linking)
VI  - 16
IP  - 1
DP  - 2024 Jan
TI  - LincR-PPP2R5C Promotes Th2 Cell Differentiation Through PPP2R5C/PP2A by Forming 
      an RNA-DNA Triplex in Allergic Asthma.
PG  - 71-90
LID - 10.4168/aair.2024.16.1.71 [doi]
AB  - 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.
CI  - Copyright (c) 2024 The Korean Academy of Asthma, Allergy and Clinical Immunology * 
      The Korean Academy of Pediatric Allergy and Respiratory Disease.
FAU - Ji, Ningfei
AU  - Ji N
AUID- ORCID: 0000-0002-5044-2240
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Chen, Zhongqi
AU  - Chen Z
AUID- ORCID: 0000-0003-1908-5262
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Wang, Zhengxia
AU  - Wang Z
AUID- ORCID: 0000-0003-1325-124X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Sun, Wei
AU  - Sun W
AUID- ORCID: 0009-0008-4178-8494
AD  - Department of Respiratory and Critical Care Medicine, Xishan People's Hospital of 
      Wuxi City, Wuxi Branch of Zhongda Hospital Affiliate to Southeast University, 
      Wuxi, China.
FAU - Yuan, Qi
AU  - Yuan Q
AUID- ORCID: 0009-0008-7985-9235
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Zhang, Xijie
AU  - Zhang X
AUID- ORCID: 0009-0009-9946-9784
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Jia, Xinyu
AU  - Jia X
AUID- ORCID: 0000-0002-1832-9504
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Wu, Jingjing
AU  - Wu J
AUID- ORCID: 0009-0006-0206-7876
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Jiang, Jingxian
AU  - Jiang J
AUID- ORCID: 0009-0007-6566-1001
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Song, Meijuan
AU  - Song M
AUID- ORCID: 0000-0002-1244-0375
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Xu, Tingting
AU  - Xu T
AUID- ORCID: 0000-0001-9892-7952
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Liu, Yanan
AU  - Liu Y
AUID- ORCID: 0000-0002-6327-344X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Ma, Qiyun
AU  - Ma Q
AUID- ORCID: 0000-0002-3726-5147
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Sun, Zhixiao
AU  - Sun Z
AUID- ORCID: 0000-0002-7364-235X
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China.
FAU - Bao, Yanmin
AU  - Bao Y
AUID- ORCID: 0000-0003-2610-2542
AD  - Department of Respiratory Medicine, Shenzhen Children's Hospital, Shenzhen, 
      China.
FAU - Zhang, Mingshun
AU  - Zhang M
AUID- ORCID: 0000-0001-5925-0168
AD  - Jiangsu Province Engineering Research Center of Antibody Drugs, NHC Key 
      Laboratory of Antibody Technique, Department of Immunology, Nanjing Medical 
      University, Nanjing, China. mingshunzhang@njmu.edu.cn.
FAU - Huang, Mao
AU  - Huang M
AUID- ORCID: 0000-0002-2743-1017
AD  - Department of Respiratory and Critical Care Medicine, The First Affiliated 
      Hospital of Nanjing Medical University, Nanjing, China. hm6114@163.com.
LA  - eng
GR  - 2016YFC0905800/Precision Medicine Research of the National Key Research and 
      Development Plan of China/China
GR  - 81770031/NSFC/National Natural Science Foundation of China/China
GR  - 81970031/NSFC/National Natural Science Foundation of China/China
GR  - 82171738/NSFC/National Natural Science Foundation of China/China
GR  - 81671563/NSFC/National Natural Science Foundation of China/China
GR  - BK20171501/Natural Science Foundation of Jiangsu Province/China
GR  - BK2017080/Natural Science Foundation of Jiangsu Province/China
GR  - BK20181497/Natural Science Foundation of Jiangsu Province/China
GR  - QNRC2016600/Jiangsu Province's Young Medical Talent Program/China
GR  - Q2017001/Jiangsu Provincial Health and Family Planning Commission 
      Foundation/China
PT  - Journal Article
PL  - Korea (South)
TA  - Allergy Asthma Immunol Res
JT  - Allergy, asthma & immunology research
JID - 101518382
PMC - PMC10823138
OTO - NOTNLM
OT  - LncRNA
OT  - Th2 cells
OT  - asthma
OT  - inflammation
OT  - protein phosphatase 2
COIS- There are no financial or other issues that might lead to conflict of interest.
EDAT- 2024/01/24 00:42
MHDA- 2024/01/24 00:43
PMCR- 2024/01/01
CRDT- 2024/01/23 18:27
PHST- 2023/03/05 00:00 [received]
PHST- 2023/08/13 00:00 [revised]
PHST- 2023/08/22 00:00 [accepted]
PHST- 2024/01/24 00:43 [medline]
PHST- 2024/01/24 00:42 [pubmed]
PHST- 2024/01/23 18:27 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 16.71 [pii]
AID - 10.4168/aair.2024.16.1.71 [doi]
PST - ppublish
SO  - Allergy Asthma Immunol Res. 2024 Jan;16(1):71-90. doi: 10.4168/aair.2024.16.1.71.