Evidence mapPaperPMID 41310622Full record

ArticleJournal of neuroinflammation2025

Inhibition of bruton's tyrosine kinase directly alleviates pathogenic CD4+ T cell response via PPAR-γ signaling in autoimmune uveitis.

Zhiqiang Xiao, Zhuang Li, Wenjie Zhu, Guanyu Chen, Xiaoshuang Luo, Zhiqing Mai, Minzhen Wang, Haixiang Huang, Zuoyi Li, Yuxun Shi and 4 more

Abstract read
In one paragraph

Article in Journal of neuroinflammation, 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

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

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

14 authors.

Zhiqiang Xiao *State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Zhuang Li *State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Wenjie Zhu *State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Guanyu Chen *State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Xiaoshuang Luo *State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Zhiqing Mai *State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Minzhen WangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Haixiang HuangShenzhen Eye Medical Center, Shenzhen Eye Hospital, Southern Medical University, Shenzhen, 518040, China.
Zuoyi LiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Yuxun ShiState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Yanyan XieState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Hao WuState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Xiaoqing ChenState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China.
Dan LiangState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-sen University, Guangzhou, 510060, China. liangdan@gzzoc.com.

Funding

Guangzhou Basic Research Program City-University Joint Foundation NO.SL2024A03J00513the Guangdong Basic and Applied Basic Research Foundation NO.2023A1515110965the National Natural Science Foundation of China NO.82401243the National Natural Science Foundation of China NO.82401245the National Natural Science Foundation of China NO.U22A20308
6 · The paper itself

Abstract

backgroundBruton’s tyrosine kinase (BTK), a key regulator of immune responses, has been extensively studied in B cells and innate immunocytes. Small-molecule BTK inhibitors (BTKi) have shown remarkable efficacy in multiple preclinical and clinical studies for autoimmune diseases via mediating the activation of B cells and innate immunocytes. Recent studies have demonstrated functional BTK expression in T cells, contributing to T cell activation and the pathogenesis of aplastic anemia. Whether BTK is involved in uveitis, the CD4+ T cell-mediated autoimmune disease, and whether it could be a therapeutic target remain unclear.

methodsWe assessed BTK expression and phosphorylation levels in CD4+ T cells from Autoimmune uveitis (AU) patients and experimental autoimmune uveitis (EAU) mice. By administering BTKi to EAU mice, we evaluated its effects on ocular and systemic inflammation levels through fundus photography, histopathology, qPCR, and flow cytometry. In vitro, we assessed its impact on the Th1/Th17/Treg differentiation, and the pathogenicity of CD4+ T cells. Transcriptomic sequencing and flow cytometry were employed to explore the potential mechanism by which BTK regulates CD4+ T cells.

resultsBTK expression and activation were upregulated in CD4+ T cells from AU patients and EAU mice. BTK inhibition suppressed the polarization of Th17 and Th1 cells, but not Treg differentiation. BTK inhibition upregulated the PPAR-γ signaling, alleviating oxidative stress and inflammatory responses in CD4+ T cells, thereby reducing ocular and systemic inflammation in EAU mice. Additionally, BTKi exhibited significant anti-inflammatory effects in CD4+ T cells from AU patients.

conclusionThis study demonstrates the critical role of BTK in CD4+ T cell-driven AU. BTK inhibition ameliorates oxidative stress and inflammatory responses via PPAR-γ involved signaling in CD4+ T cells and suppresses their differentiation to Th1/Th17 to restore immune homeostasis, thereby mitigating AU. These findings identify BTK as a potential therapeutic target and provide a theoretical foundation for the clinical application of BTKi in AU.

Indexed as

Agammaglobulinaemia Tyrosine KinaseAutoimmune DiseasesCD4-Positive T-LymphocytesPPAR gammaProtein Kinase InhibitorsUveitisAnimalsFemaleHumansMaleMiceMice, Inbred C57BLSignal TransductionAgammaglobulinaemia Tyrosine KinaseBTK protein, humanBtk protein, mousePPAR gammaProtein Kinase InhibitorsAutoimmune uveitisBTKCD4 + T cellInflammationOxidative stressPPAR-γSmall-molecule BTK inhibitors

Identifiers

PMID41310622
PMCPMC12751244

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.