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

Ziyin YANG; Lei HAI; Xiaoyu CHEN; Siwen WU; Yan LV; Dawei CUI; Jue XIE

doi:10.1631/jzus.B2300947

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

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Research Article | Updated：2025-03-13

OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia
OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia
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
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 3, Pages: 240-253(2025)
Affiliations：

Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Funds：
DOI：10.1631/jzus.B2300947
CLC：
CSTR：
Received：07 January 2024，

Revised：15 February 2024，

Published Online：06 March 2025，

Published：13 March 2025
Accepted：

杨子吟,海蕾,陈小瑜等.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[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(03):240-253.

Ziyin YANG, Lei HAI, Xiaoyu CHEN, et al. OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(3): 240-253.
杨子吟,海蕾,陈小瑜等.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[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(03):240-253. DOI： 10.1631/jzus.B2300947.

Ziyin YANG, Lei HAI, Xiaoyu CHEN, et al. OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(3): 240-253. DOI： 10.1631/jzus.B2300947.

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，

OX40L

和

OX40

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。

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 of

OX40L

and

OX40

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) i

n 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.

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references

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