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On-line Access: 2025-03-13

Received: 2024-01-07

Revision Accepted: 2024-02-15

Crosschecked: 2025-03-13

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Jue XIE

https://orcid.org/0000-0002-4270-671X

Ziyin YANG

https://orcid.org/0000-0001-8542-1688

Lei HAI

https://orcid.org/0000-0002-5474-5492

Dawei CUI

https://orcid.org/0000-0003-3840-1486

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Journal of Zhejiang University SCIENCE B 2025 Vol.26 No.3 P.240-253

http://doi.org/10.1631/jzus.B2300947


OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia


Author(s):  Ziyin YANG, Lei HAI, Xiaoyu CHEN, Siwen WU, Yan LV, Dawei CUI, Jue XIE

Affiliation(s):  Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine,Hangzhou310003,China

Corresponding email(s):   zyyyxj2011@zju.edu.cn, daweicui@zju.edu.cn

Key Words:  OX40, OX40 ligand (OX40L), Immune thrombocytopenia, Follicular helper T (Tfh) cell, B cell


Ziyin YANG, Lei HAI, Xiaoyu CHEN, Siwen WU, Yan LV, Dawei CUI, Jue XIE. OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia[J]. Journal of Zhejiang University Science B, 2025, 26(3): 240-253.

@article{title="OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia",
author="Ziyin YANG, Lei HAI, Xiaoyu CHEN, Siwen WU, Yan LV, Dawei CUI, Jue XIE",
journal="Journal of Zhejiang University Science B",
volume="26",
number="3",
pages="240-253",
year="2025",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300947"
}

%0 Journal Article
%T OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia
%A Ziyin YANG
%A Lei HAI
%A Xiaoyu CHEN
%A Siwen WU
%A Yan LV
%A Dawei CUI
%A Jue XIE
%J Journal of Zhejiang University SCIENCE B
%V 26
%N 3
%P 240-253
%@ 1673-1581
%D 2025
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300947

TY - JOUR
T1 - OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia
A1 - Ziyin YANG
A1 - Lei HAI
A1 - Xiaoyu CHEN
A1 - Siwen WU
A1 - Yan LV
A1 - Dawei CUI
A1 - Jue XIE
J0 - Journal of Zhejiang University Science B
VL - 26
IS - 3
SP - 240
EP - 253
%@ 1673-1581
Y1 - 2025
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300947


Abstract: 
immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression ofOX40L andOX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.

OX40配体促进免疫性血小板减少症小鼠的滤泡辅助性T细胞分化和发育

杨子吟,海蕾,陈小瑜,吴四稳,吕燕,崔大伟,谢珏
浙江大学医学院附属第一医院输血科,中国杭州市,310003
摘要:免疫性血小板减少症(ITP)是以抗体介导血小板损伤为特征的出血性自身免疫性疾病,其病理机制复杂,有待进一步阐明。共刺激分子肿瘤坏死因子受体超家族成员4(OX40)和OX40配体(OX40L)在自身免疫性疾病的致病机制中发挥着重要作用。前期研究发现,OX40LOX40在ITP患者外周血单个核细胞(PBMCs)中表达显著升高。本研究结果显示:OX40L可在体外诱导滤泡辅助性T(Tfh)细胞活化,上调诱导性共刺激分子(ICOS)、程序性细胞死亡蛋白1(PD-1)和CD40配体(CD40L)的表达;OX40L?OX40的异常表达可能通过增强Tfh细胞对B淋巴细胞的辅助功能,促进Tfh1向Tfh2的转型,以及诱导自身抗体产生,从而加速ITP进展;OX40L?OX40轴的信号转导可能与肿瘤坏死因子受体相关因子(TRAF)?核因子κB(NF-κB)和Janus 激酶(JAK)?信号转导与转录激活因子(STAT)信号通路的激活有关。综上所述,OX40L?OX40信号通路是ITP的新型潜在治疗靶点。

关键词:肿瘤坏死因子受体超家族成员4(OX40);OX40配体(OX40L);免疫性血小板减少症(ITP);滤泡辅助性T(Th)细胞;B细胞

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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