Evidence map›Paper›PMID 40681714›Full record

ArticleClinical rheumatology2025

NETs promote fibroblast-like synoviocytes producing IL-6 to enhance T follicular helper cell response in rheumatoid arthritis.

Zijia Li, Yali Liu, Yan Zhang, Zhichun Zhang, Shangwen Lei, Haili Shen

Abstract read
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In one paragraph

Article in Clinical rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. 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

6 authors.

Zijia LiDepartment of Rheumatology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.ORCID http://orcid.org/0009-0006-9901-4024
Yali LiuCuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Yan ZhangDepartment of Rheumatology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
Zhichun ZhangDepartment of Rheumatology, Gansu Provincial Hospital, Lanzhou, 730000, Gansu, China.
Shangwen LeiDepartment of Rheumatology, Gansu Provincial Hospital, Lanzhou, 730000, Gansu, China.
Haili ShenDepartment of Rheumatology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China. shenhl@lzu.edu.cn.

Funding

Gansu University of Chinese Medicine No. GZKP-2022-24National Research Council of the Philippines No.23JRRA1510Natural Science Foundation of Gansu Province No.22JR5RA661
6 · The paper itself

Abstract

objectiveAlthough neutrophil extracellular traps (NETs) are recognized as key contributors to rheumatoid arthritis (RA) progression, their immunomodulatory effects on T follicular helper (Tfh) cell differentiation remain enigmatic. Based on the effect of NETs on RA fibroblast-like synoviocytes (RA-FLSs), our study is aimed at investigating the effect of NETs on Tfh cell differentiation in RA.

methodsImmunofluorescence, western blotting, and flow cytometry were used to investigate whether NETs mediated the inflammatory phenotype transformation of synovium fibroblasts to produce IL-6 and promote Tfh cell differentiation through TLR9/MyD88/NF-κB pathway. The expressions of Cit H3, MPO, TLR9, and Bcl-6 in the synovial tissues of the trauma control group and the RA group were analyzed by immunohistochemistry.

resultsOur findings indicated that the plasma concentrations of IL-6 and MPO-DNA in RA patients were positively correlated with the level of IL-21 in lymphocytes and the proportion of circulating T follicular helper cells in peripheral blood. Further analysis revealed that NETs mediate the release of IL-6 from RA-FLSs through the TLR9/MyD88/NF-κB pathway, thereby inducing the differentiation of CD4 + T cells into Tfh cells and promoting the development of adaptive immunity in RA.

conclusionThis study demonstrated that NETs promoted Tfh cell differentiation by inducing IL-6 production by synovial fibroblasts through the TLR9/MyD88/NF-κB pathway. Targeting TLR9 may be a potential target for the treatment of RA. Key Points • NETs promoted Tfh cell differentiation by inducing IL-6 production by synovial fibroblasts through the TLR9/MyD88/NF-κB pathway. • Targeting TLR9 may be a potential target for the treatment of RA.

Indexed as

Arthritis, RheumatoidExtracellular TrapsInterleukin-6SynoviocytesT Follicular Helper CellsAdultCell DifferentiationFemaleFibroblastsHumansInterleukin-21InterleukinsMaleMiddle AgedMyeloid Differentiation Factor 88NF-kappa BIL6 protein, humanInterleukin-21Interleukin-6InterleukinsMYD88 protein, humanMyeloid Differentiation Factor 88NF-kappa BTLR9 protein, humanToll-Like Receptor 9Interleukin-6 (IL-6)Neutrophil extracellular traps (NETs)T follicular helper (Tfh) cellToll-like receptor 9 (TLR9)

Identifiers

PMID40681714

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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.