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

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.