IL-33 regulates abnormally increased expression of ST2 in bone marrow follicular helper T cell in SLE with hematological abnormalities

IF 3.8 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2025-06-24 DOI:10.1016/j.clim.2025.110550

Shaowei Pan , Xiaoyun Xie , Tong Li , Shiyao Wu , Ying Jiang , Huali Zhang , Xiaoli Zhang

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Abstract

Systemic lupus erythematosus (SLE) is often accompanied by hematological complications, with T follicular helper (Tfh) cells playing a pivotal role in its pathogenesis. This study explores the relationship between bone marrow Tfh and Interleukin-33 (IL-33) in SLE patients with hematological abnormalities. Using flow cytometry and ELISA, we found elevated percentages of bone marrow ST2+ Tfh cells in SLE patients, which correlated with disease activity, white blood cell count, and B cell percentage. Increased bone marrow IL-33 and BLyS levels were also observed. Keyhole-limpet hemocyanin (KLH)-immunized mouse model demonstrated IL-33-dependent Tfh expansion, while ST2 knockdown reduced Tfh frequency. In vitro co-culture experiments demonstrated that the IL-33/ST2 axis plays a pivotal role in enhancing the function of Tfh and T peripheral helper (Tph) cells, thereby promoting B cell differentiation into antibody-secreting plasma cells. These findings establish IL-33/ST2 as a key regulator of humoral immunity and a potential therapeutic target for SLE.

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IL-33调节SLE伴血液学异常患者骨髓滤泡辅助T细胞ST2表达异常升高。

系统性红斑狼疮（SLE）常伴有血液学并发症，T滤泡辅助细胞（Tfh）在其发病机制中起关键作用。本研究探讨血液学异常SLE患者骨髓Tfh与白细胞介素-33 （IL-33）的关系。通过流式细胞术和ELISA，我们发现SLE患者骨髓ST2+ Tfh细胞百分比升高，其与疾病活动性、白细胞计数和B细胞百分比相关。骨髓IL-33和BLyS水平升高。Keyhole-limpet hemocyanin （KLH）免疫小鼠模型显示il -33依赖性Tfh扩增，而ST2敲除可降低Tfh频率。体外共培养实验表明，IL-33/ST2轴在增强Tfh和T外周辅助细胞（Tph）的功能，从而促进B细胞向分泌抗体的浆细胞分化中起关键作用。这些发现表明IL-33/ST2是体液免疫的关键调节因子和SLE的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.