Evidence map›Paper›PMID 33568199›Full record

ArticleClinical epigenetics2021

UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE.

Limin Liu, Longyuan Hu, Linxuan Yang, Sujie Jia, Pei Du, Xiaoli Min, Jiali Wu, Haijing Wu, Hai Long, Qianjin Lu and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.1field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
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  7. Article
  8. Review
  9. Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Endosome Traffic Modulates Pro-Inflammatory Signal Transduction in CD4International journal of molecular sciences · 2023
    Review
  16. Review
  17. Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.Clinical reviews in allergy & immunology · 2022
    Review
  18. Review
  19. Article
  20. The RING finger protein family in health and disease.Signal transduction and targeted therapy · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Limin Liu *Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Longyuan Hu *Department of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Linxuan YangDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Sujie JiaDepartment of Pharmacy, Central South University, The Third Xiangya Hospital, Changsha, China.
Pei DuDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Xiaoli MinDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Jiali WuDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Haijing WuDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Hai LongDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Qianjin LuDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China.
Ming ZhaoDepartment of Dermatology, Second Xiangya Hospital, Central South University, #139 Renmin Middle Road, Changsha, 410011, Hunan, China. zhaoming307@csu.edu.cn.ORCID 0000-0002-7874-8743
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTranscription factor B cell lymphoma 6 (BCL6) is a master regulator of T follicular helper (Tfh) cells, which play a crucial role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanisms by which BCL6 expression is regulated are poorly understood. Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is an important epigenetic factor that regulates DNA methylation and histone modifications. In the present study, we assessed whether UHRF1 can regulate BCL6 expression and influence the differentiation and proliferation of Tfh cells.

resultsCompared to healthy controls, the mean fluorescence intensity of UHRF1 (UHRF1-MFI) in Tfh cells from SLE patients was significantly downregulated, whereas that of BCL6 (BCL6-MFI) was significantly upregulated. In vitro, UHRF1 knockdown led to BCL6 overexpression and promoted Tfh cell differentiation. In contrast, UHRF1 overexpression led to BCL6 downregulation and decreased Tfh cell differentiation. In vivo, conditional UHRF1 gene knockout (UHRF1-cKO) in mouse T cells revealed that UHRF1 depletion can enhance the proportion of Tfh cells and induce an augmented GC reaction in mice treated with NP-keyhole limpet hemocyanin (NP-KLH). Mechanistically, UHRF1 downregulation can decrease DNA methylation and H3K27 trimethylation (H3K27me3) levels in the BCL6 promoter region of Tfh cells.

conclusionsOur results demonstrated that UHRF1 downregulation leads to increased BCL6 expression by decreasing DNA methylation and H3K27me3 levels, promoting Tfh cell differentiation in vitro and in vivo. This finding reveals the role of UHRF1 in regulating Tfh cell differentiation and provides a potential target for SLE therapy.

Indexed as

AnimalsCCAAT-Enhancer-Binding ProteinsCell DifferentiationDNA MethylationDown-RegulationEpigenomicsFemaleGene Expression RegulationHaptensHemocyaninsHistone CodeHumansLupus Erythematosus, SystemicMaleMicePromoter Regions, Genetic4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyaninBCL6 protein, humanBcl6 protein, mouseCCAAT-Enhancer-Binding ProteinsHaptensHemocyaninsProto-Oncogene Proteins c-bcl-6Transcription FactorsUbiquitin-Protein LigasesUHRF1 protein, humanUhrf1 protein, mouseBCL6EpigeneticsSystemic lupus erythematosusTfh cellsUHRF1

Identifiers

PMID33568199
PMCPMC7874639
OpenAlexW3127318266

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.