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

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

doi:10.1016/j.clim.2025.110550

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

Clin Immunol. 2025 Jun 24:110550. doi: 10.1016/j.clim.2025.110550. Online ahead of print.

Authors

Shaowei Pan¹, Xiaoyun Xie², Tong Li², Shiyao Wu², Ying Jiang², Huali Zhang³, Xiaoli Zhang²

Affiliations

¹ The Department of Rheumatology and Immunology, Xiangya hospital of Central South University, Changsha, China; The Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, China.
² The Department of Rheumatology and Immunology, Xiangya hospital of Central South University, Changsha, China; Provincial Clinical Research Center for Rheumatic and immunologic Diseases, Xiangya Hospital, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.
³ The Department of Pathophysiology, School of Basic Medicine Science, Central South University, Changsha, China; Sepsis Translational Medicine Key Laboratory of Hunan Province, Central South University, Changsha, China; National Medicine Functional Experimental Teaching Center, Central South University, Changsha, China.

PMID: 40571239
DOI: 10.1016/j.clim.2025.110550

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.

Keywords: Follicular helper T cell; Interleukin-33; Systemic lupus erythematosus.