Evidence map›Paper›PMID 41381571›Full record

ArticleNature communications2025

Lactate bridges mesangial cells to the differentiation of follicular helper T cells in lupus nephritis.

Mengdi Liu, Huiyan Ji, Jiaxin Lei, Ming Zheng, Lingyi Li, Xingyu Zhai, Hongmin Wang, Ting Liu, Qinghua Cao, Lin Xu and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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.

Mengdi LiuThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Huiyan JiThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Jiaxin LeiThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Ming ZhengThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Lingyi LiThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Xingyu ZhaiThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Hongmin WangThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China.
Ting LiuDepartment of Rheumatology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China.
Qinghua CaoRenal Medicine, Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, St Leonards, New South Wales, Australia.
Lin XuDepartment of Immunology, Zunyi Medical University, Zunyi, China.ORCID http://orcid.org/0000-0002-6889-0279
Zhenke WenThe Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China. zkwen@suda.edu.cn.ORCID http://orcid.org/0000-0003-0542-0349

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lupus nephritis (LN), a serious complication of systemic lupus erythematosus, is characterized by the deposition of IgG immune complexes. The generation of these autoantibodies depends on T follicular helper (Tfh) cells within secondary lymphoid organs. However, the potential contribution of Tfh cells residing within the kidney has remained unexplored. Here, our analysis of a single-cell kidney dataset from LN patients, alongside studies in humanized chimeras and kidney organoids, identifies the accumulation of renal Tfh cells. Mechanistically, self-DNA-stimulated LN-associated mesangial cells (MC) promote Tfh differentiation by inducing CNBP-mediated MPC1 deficiency, leading to increased lactate production. In turn, elevated lactate levels enhance PCAF-catalyzed BCL6 lactylation and subsequent K6- and K29-linked ubiquitination at Lys430, preventing proteasomal degradation of BCL6. Stabilization of BCL6 ultimately reinforces Tfh differentiation, amplifying renal autoimmune responses. Importantly, targeted depletion of Tfh cells mitigates disease progression in humanized chimeras. Thus, our findings reveal a tissue program of Tfh differentiation within the autoimmune kidney microenvironment, identifying a potential therapeutic target for the management of LN.

Indexed as

Cell DifferentiationLupus NephritisMesangial CellsT Follicular Helper CellsT-Lymphocytes, Helper-InducerAnimalsFemaleHumansKidneyMiceProto-Oncogene Proteins c-bcl-6UbiquitinationBCL6 protein, humanProto-Oncogene Proteins c-bcl-6

Identifiers

PMID41381571
PMCPMC12816631

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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.