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231226s2023 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2023.109323
|2 doi
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|a pubmed24n1184.xml
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|a (DE-627)NLM355241285
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|a (NLM)37019422
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|a (PII)S1521-6616(23)00102-X
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|a DE-627
|b ger
|c DE-627
|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Zhang, Wanyun
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a TET2-mediated upregulation of 5-hydroxymethylcytosine in LRRC39 promoter promotes Th1 response in association with downregulated Treg response in Vogt-Koyanagi-Harada disease
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|c 2023
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| 336 |
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 01.05.2023
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|a Date Revised 07.05.2023
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2023 Elsevier Inc. All rights reserved.
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|a DNA 5-Hydroxymethylcytosine (5-hmC), an oxidative reaction mediated by the ten-eleven translocation (TET) family, has been reported to play an essential role in the progression of auto-inflammatory and autoimmune diseases. By far, little is known about the effect of DNA 5-hmC and the TET family on the development of Vogt-Koyanagi-Harada (VKH) disease. In this study, we discovered that the global DNA 5-hmC level and the TET activity were elevated in association with the up-regulated expression of TET2 at both mRNA and protein levels in CD4+T cells from active VKH patients compared to healthy controls. Integrated analysis of DNA 5-hmC pattern and transcription profile of CD4+ T cells revealed that 6 candidate target genes were involved in the development of VKH disease. The promoter 5-hmC and mRNA levels of leucine rich repeat containing 39 (LRRC39) were verified to be elevated in active VKH patients. Functional experiments showed that TET2 could up-regulate LRRC39 mRNA expression by increasing the promoter 5-hmC level of LRRC39 in CD4+ T cells from active VKH patients. Up-regulated LRRC39 expression could increase the frequencies of IFN-γ+ and IL-17+ CD4+ T cells as well as the secretions of IFN-γ and IL-17 in association with the decreased frequency of CD4+CD25+FOXP3+ regulatory T (Treg) cells and the reduced production of IL-10. Additionally, restoration of LRRC39 rescued TET2-silencing-mediated reduced frequency of IFN-γ+ CD4+ T cells and increased frequency of CD4+CD25+FOXP3+ Treg cells. Collectively, our study reveals a novel axis, the TET2-5-hmC-LRRC39-Th1/Treg responses axis, in the pathogenesis of VKH and provides a potential target for further investigation into the epigenetic therapy of this disease
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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| 650 |
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|a 5-hmC
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| 650 |
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|a Autoimmune disease
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| 650 |
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4 |
|a LRRC39
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| 650 |
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|a TET2
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| 650 |
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|a Transcriptomics
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| 650 |
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4 |
|a VKH disease
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| 650 |
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|a 5-hydroxymethylcytosine
|2 NLM
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| 650 |
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|a 1123-95-1
|2 NLM
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| 650 |
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|a Dioxygenases
|2 NLM
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| 650 |
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7 |
|a EC 1.13.11.-
|2 NLM
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| 650 |
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|a DNA-Binding Proteins
|2 NLM
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| 650 |
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7 |
|a Forkhead Transcription Factors
|2 NLM
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| 650 |
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7 |
|a Interleukin-17
|2 NLM
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| 650 |
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|a RNA, Messenger
|2 NLM
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| 650 |
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|a TET2 protein, human
|2 NLM
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| 650 |
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7 |
|a EC 1.13.11.-
|2 NLM
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| 650 |
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|a LRRC39 protein, human
|2 NLM
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| 700 |
1 |
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|a Chen, Zhijun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yi, Kun
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Su, Guannan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Liu, Yaning
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Deng, Yang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhang, Yinan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cao, Qingfeng
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Pu, Yanlin
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Luo, Xiang
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Lai, Yujie
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yang, Peizeng
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 250(2023) vom: 01. Mai, Seite 109323
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
8 |
|g volume:250
|g year:2023
|g day:01
|g month:05
|g pages:109323
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| 856 |
4 |
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|u http://dx.doi.org/10.1016/j.clim.2023.109323
|3 Volltext
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|a SYSFLAG_A
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|a GBV_NLM
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|a GBV_ILN_11
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|a GBV_ILN_24
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|a GBV_ILN_350
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|a AR
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|d 250
|j 2023
|b 01
|c 05
|h 109323
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