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

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

Author: Ziyin YANG ¹ ; Lei HAI ¹ ; Xiaoyu CHEN ¹ ; Siwen WU ¹ ; Yan LV ¹ ; Dawei CUI ² ; Jue XIE ³
Author Information

1. Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
2. Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. daweicui@zju.edu.cn.
3. Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. zyyyxj2011@zju.edu.cn.
Publication Type:Journal Article
Keywords: B cell; Follicular helper T (Tfh) cell; Immune thrombocytopenia; OX40; OX40 ligand (OX40L)
MeSH: Animals; OX40 Ligand/physiology*; Purpura, Thrombocytopenic, Idiopathic/immunology*; Cell Differentiation; Mice; T-Lymphocytes, Helper-Inducer/cytology*; T Follicular Helper Cells/cytology*; Signal Transduction; Receptors, OX40; Mice, Inbred C57BL; Humans; Female
From: Journal of Zhejiang University. Science. B 2025;26(3):240-253
CountryChina
Language:English
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) 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.