Evidence map›Paper›PMID 40517268›Full record

ArticleArthritis research & therapy2025

Enhanced cytotoxicity of aging associated NKG2C + CD8 + T cells in ankylosing spondylitis via HLA-B27.

Kunhai Tang, Xiaobei Ma, Jian Gao, Lilu Zu, Yanyun Ma, Dachun Zhuo, Chenyuan Wu, Yulong Tang, Feng Qian, Li Jin and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthritis research & therapy, 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

13 authors.

Kunhai Tang *State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Science, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
Xiaobei Ma *State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Jian GaoZhangjiang Fudan International Innovation Center, Human Phenome Institute, Fudan University, Shanghai, China.
Lilu ZuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Science, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
Yanyun MaDepartment of Anthropology and Human Genetics, Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
Dachun ZhuoState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Science, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
Chenyuan WuState Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Yulong TangState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Science, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China.
Feng QianZhangjiang Fudan International Innovation Center, Human Phenome Institute, Fudan University, Shanghai, China.
Li JinState Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China.
Jiucun WangState Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, China. jcwang@fudan.edu.cn.
Qi ZhuInstitute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Guanghua Integrative Medicine Hospital, Shanghai, China. zhuqigh540@126.com.
Jing LiuState Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Science, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Fudan University, Shanghai, China. liu_jing@fudan.edu.cn.

Funding

CAMS Innovation Fund for Medical Sciences 2019-I2M-5-066National Key Research and Development programme of China 2024YFC3405800National Natural Science Foundation of China 82001726Science and Technology Commission of Shanghai Municipality 19JC1411702Scientific research project of Shanghai Health Commission 202040396Shanghai Municipal Science and Technology Major Project 2017SHZDZX01Shanghai Natural Science Foundation 21ZR1454400
6 · The paper itself

Abstract

backgroundThis study aims to explore the common mechanisms between aging and the pathogenesis of ankylosing spondylitis (AS) and to identify potential therapeutic targets.

methodsA total of 87 patients with AS and matched controls were analyzed via multidimensional flow cytometry to examine the peripheral blood immune signature. Single-cell RNA sequencing was employed to characterize T-cell subsets. The infiltration of Ly49h + cells (the murine homolog of NKG2C) was observed in a collagen-induced arthritis mouse model, and functional experiments were conducted to validate the cytotoxicity of NKG2C + CD8 + T cells. The mechanisms were further confirmed via the use of HLA-B27 transgenic mice and RNA-sequencing.

resultsThe peripheral blood immune signature of AS patients exhibited dysregulation similar to that observed during aging. NKG2C + CD8 + T cells activated the PI3K‒Akt signaling pathway and increased phagocytosis in AS patients. HLA-B27 stimulation significantly increased the cytotoxicity of this subset, an effect that could be reversed by NKG2C blockade. In HLA-B27 transgenic mice, Ly49h + T cells exhibited significantly enhanced degranulation ability. RNA sequencing validated the activation of the PI3K‒Akt pathway in NKG2C + CD8 + T cells by HLA-B27.

conclusionsHLA-B27 drives the cytotoxicity of aging-related NKG2C + CD8 + T cells via activation of the PI3K‒Akt signaling pathway. Targeting NKG2C inhibition may represent a novel therapeutic strategy for AS. This study elucidates the association between immune aging and the pathogenesis of AS, providing theoretical evidence for clinical intervention.

Indexed as

AgingCD8-Positive T-LymphocytesCytotoxicity, ImmunologicHLA-B27 AntigenNK Cell Lectin-Like Receptor Subfamily CSpondylitis, AnkylosingAdultAnimalsArthritis, ExperimentalFemaleHumansMaleMiceMice, TransgenicMiddle AgedHLA-B27 AntigenNK Cell Lectin-Like Receptor Subfamily CAnkylosing Spondylitis (AS)ImmunosenescenceSignal Transduction PathwaysTherapeutic Strategies

Identifiers

PMID40517268
PMCPMC12166590

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.