Evidence map›Paper›PMID 40506739›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

Reciprocal METTL3-PAX5 regulation in maintaining B-cell identity and promoting B-cell hyperreactivity in SLE.

Yiying Yang, Ying Zhang, Shasha Xie, Ke Liu, Meidong Liu, Yisha Li, Hui Luo, Xiaoxia Zuo, Huali Zhang, Muyao Guo

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. RNA mActa pharmacologica Sinica · 2026
    Review
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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

10 authors.

Yiying YangDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Ying ZhangDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Shasha XieDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Ke LiuDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Meidong LiuDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Yisha LiDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Hui LuoDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Xiaoxia ZuoDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
Huali ZhangDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. zhanghuali@csu.edu.cn.
Muyao GuoDepartment of Rheumatology, Xiangya Hospital, Department of Pathophysiology, Xiangya School of Basic Medical Sciences, Central South University, Changsha, Hunan, China. gmuyao@csu.edu.cn.

Funding

China Postdoctoral Science Foundation 2024M753695National Natural Science Foundation of China 81901664National Natural Science Foundation of China 82070018Natural Science Foundation of Hunan Province 2020JJ5894Natural Science Foundation of Hunan Province 2025JJ60571
6 · The paper itself

Abstract

objectiveMETTL3, an m6A methyltransferase, enhances germinal center responses. This study explores its role in lupus B cells and its impact on B-cell activation.

methodsMETTL3 and m6A levels in B cells from systemic lupus erythematosus (SLE) patients and lupus-prone mice were analyzed using m6A dot blot, RT-qPCR, western blotting, and flow cytometry. B-cell activation and differentiation were induced with lipopolysaccharide (LPS). The effects of METTL3 overexpression or inhibition on B-cell maturation were assessed in vivo. In Raji B cells, METTL3 and PAX5 knockdowns were performed to examine their regulatory relationship. EMSA and dual-luciferase assays confirmed PAX5 binding to the METTL3 promoter, while RIP and actinomycin D assays evaluated METTL3’s interaction with PAX5 mRNA. MeRIP-seq profiled m6A modifications across B-cell subsets.

resultsMETTL3 expression and m6A levels were significantly elevated in B cells from SLE patients, with METTL3 levels positively correlating with disease activity. Elevated m6A and METTL3 levels were observed in both naïve and activated B cells but decreased markedly during differentiation into ASCs, both in vivo and in vitro. MeRIP-seq analysis identified distinct m6A methylation patterns among B-cell subsets, particularly in key transcription factors critical for B-cell activation and differentiation. METTL3 facilitated pre-B cell development in bone marrow and maintained the balance of splenic B-cell subsets in mice. Furthermore, METTL3 preserved B-cell identity and enhanced activation. Mechanistically, METTL3 bound to PAX5 mRNA, stabilizing it via m6A modification and promoting PAX5 expression. In turn, PAX5 directly bound to the METTL3 promoter, driving its expression.

conclusionThe elevated expression of METTL3 in lupus B cells is linked to the maintenance of autoreactive B-cell hyperresponsiveness, contributing to the pathogenesis of SLE. The reciprocal regulation between METTL3 and PAX5 highlights a critical mechanism underlying B-cell activation and persistence in autoimmune conditions like lupus.

Indexed as

B-LymphocytesLupus Erythematosus, SystemicMethyltransferasesPAX5 Transcription FactorAnimalsCell DifferentiationEpitranscriptomeFemaleGene Expression RegulationHumansLymphocyte ActivationMiceRNA MethylationMethyltransferasesMETTL3 protein, humanPAX5 protein, humanPax5 protein, mousePAX5 Transcription FactorB cellsM6AMETTL3PAX5SLE

Identifiers

PMID40506739
PMCPMC12160386

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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 Socratic graph.